Commentary

“Drugs don’t work in patients who don’t take them.”

–C. Everett Koop, M.D.

While it would be hard to imagine accountable care organizations being able to get the data they need to manage care without electronic health records, and EHRs are critical as payment has evolved to emphasize the outcomes of treatment, one area remains the holy grail of disease management: how to get patients to take the medications that are prescribed.

Poor adherence to medications is a critical issue in the management of chronic disease. The causes for suboptimal adherence are numerous, including the cost of medications, patient-physician communication, patient education, motivation, and simple forgetfulness.

Approximately 1.5 billion prescriptions, at a cost of more than $250 billion, are dispensed each year in the United States. A large body of evidence supports the use of these medications. For patients with diabetes, for instance, correct medication use can lower blood sugar, blood pressure, and cholesterol, and by so doing, decrease morbidity and mortality from both microvascular and macrovascular disease.

The act of taking medications is influenced by many factors, and all of these factors come together at a point in time when patients are not directly engaged with the health care system. It is at that moment that patients remember and decide whether to take their medications.

Numerous studies show that individuals often do not take their medicines as prescribed. Adherence rates for medications for chronic disease show that patients on average take only about 50% of prescribed doses. For patients with diabetes, the average adherence rate is about 70%, with rates ranging in different studies from 31% to 87%.

When patients do not take their medications correctly, there can be severe consequences. Poor medication adherence can lead to poorer clinical outcomes, including increased hospitalizations. One large dataset of more than 56,000 individuals with type 2 diabetes covered by employer-sponsored health insurance showed that increased adherence to medications significantly reduced hospitalizations and emergency department visits. When adherence rates increased, the hospitalization rate fell 23%, and the rate of emergency department visits decreased 46%, resulting in significant cost savings for the health system.¹

In response to this issue, many strategies have emerged. We now regularly get correspondence from insurance companies alerting us to nonadherence of individual patients. This information tends to be of little benefit, because the information is received long after the decision to take or not take the medication is made. Our response in the office to our patients is generally to remind them to take their medications, which is not much different from the discussion we have with them without that information.

Recently, a new set of apps for smartphones and tablets has emerged to help patients organize their approach to taking medications. Examples of some of these apps include Care4Today, Dosecast, Medisafe, MedSimple, MyMedREc, MyMeds, and OnTimeRx. Most of these apps allow a patient to put in their medication schedule and are organized to provide reminders when it is time to take medications.

The problem with reminders, of course, is that they don’t always happen at a time when it is convenient for a person to take their medications. For example, if your app reminds you to take your medicines at 9 p.m. each night, and you are at the movies on a Saturday night, you may extinguish the reminder and not remember to take the medications when you get home.

Many of the apps also track adherence rates so that patients can see how well they are doing in taking their medications. The results are often startling to patients, and it is hoped that such information would encourage more effort in taking medications.

One problem with many of the apps currently available is that they essentially function as sophisticated alarm clocks. They do not get at some of the fundamental reasons that people do not take their medications, which would require more behavioral input.

In fact, a recent article in the American Journal of Preventive Medicine looked at 166 medication adherence apps and concluded that current apps contained little in the way of evidence-based behavioral change techniques that have been shown to help change behavior. In fact, only about one-third of apps contained any feedback on behavior at all.²

While adherence apps still have a way to go, they can be helpful, and many contain interesting, novel features. Some allow the patient to input the name of a medication by scanning the name from the medication’s pill bottle. Some have the ability not only to remind a patient to take a medication, but also to text that patient’s caregiver (or parent, in the case of a teenager) if the medication is not taken.

While not perfect, these adherence apps are worth learning more about. They may be helpful additions to our efforts to achieve the best outcomes for our patients by helping them to actually take the medications that we so carefully prescribe.

References

1. Encinosa, W.E.; Bernard, D.; Dor, A. Does prescription drug adherence reduce hospitalizations and costs? The case of diabetes. Advances in Health Economics and Health Services Research 22, pp. 151-73, 2010 (AHRQ Publication No. 11-R008).

2. Am J Prev Med. 2015 Nov 17. pii: S0749-3797(15)00637-6. doi: 10.1016/j.amepre.2015.09.034.

Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia.

“Drugs don’t work in patients who don’t take them.”

–C. Everett Koop, M.D.

While it would be hard to imagine accountable care organizations being able to get the data they need to manage care without electronic health records, and EHRs are critical as payment has evolved to emphasize the outcomes of treatment, one area remains the holy grail of disease management: how to get patients to take the medications that are prescribed.

Poor adherence to medications is a critical issue in the management of chronic disease. The causes for suboptimal adherence are numerous, including the cost of medications, patient-physician communication, patient education, motivation, and simple forgetfulness.

Approximately 1.5 billion prescriptions, at a cost of more than $250 billion, are dispensed each year in the United States. A large body of evidence supports the use of these medications. For patients with diabetes, for instance, correct medication use can lower blood sugar, blood pressure, and cholesterol, and by so doing, decrease morbidity and mortality from both microvascular and macrovascular disease.

The act of taking medications is influenced by many factors, and all of these factors come together at a point in time when patients are not directly engaged with the health care system. It is at that moment that patients remember and decide whether to take their medications.

Numerous studies show that individuals often do not take their medicines as prescribed. Adherence rates for medications for chronic disease show that patients on average take only about 50% of prescribed doses. For patients with diabetes, the average adherence rate is about 70%, with rates ranging in different studies from 31% to 87%.

When patients do not take their medications correctly, there can be severe consequences. Poor medication adherence can lead to poorer clinical outcomes, including increased hospitalizations. One large dataset of more than 56,000 individuals with type 2 diabetes covered by employer-sponsored health insurance showed that increased adherence to medications significantly reduced hospitalizations and emergency department visits. When adherence rates increased, the hospitalization rate fell 23%, and the rate of emergency department visits decreased 46%, resulting in significant cost savings for the health system.¹

In response to this issue, many strategies have emerged. We now regularly get correspondence from insurance companies alerting us to nonadherence of individual patients. This information tends to be of little benefit, because the information is received long after the decision to take or not take the medication is made. Our response in the office to our patients is generally to remind them to take their medications, which is not much different from the discussion we have with them without that information.

Recently, a new set of apps for smartphones and tablets has emerged to help patients organize their approach to taking medications. Examples of some of these apps include Care4Today, Dosecast, Medisafe, MedSimple, MyMedREc, MyMeds, and OnTimeRx. Most of these apps allow a patient to put in their medication schedule and are organized to provide reminders when it is time to take medications.

The problem with reminders, of course, is that they don’t always happen at a time when it is convenient for a person to take their medications. For example, if your app reminds you to take your medicines at 9 p.m. each night, and you are at the movies on a Saturday night, you may extinguish the reminder and not remember to take the medications when you get home.

Many of the apps also track adherence rates so that patients can see how well they are doing in taking their medications. The results are often startling to patients, and it is hoped that such information would encourage more effort in taking medications.

One problem with many of the apps currently available is that they essentially function as sophisticated alarm clocks. They do not get at some of the fundamental reasons that people do not take their medications, which would require more behavioral input.

In fact, a recent article in the American Journal of Preventive Medicine looked at 166 medication adherence apps and concluded that current apps contained little in the way of evidence-based behavioral change techniques that have been shown to help change behavior. In fact, only about one-third of apps contained any feedback on behavior at all.²

While adherence apps still have a way to go, they can be helpful, and many contain interesting, novel features. Some allow the patient to input the name of a medication by scanning the name from the medication’s pill bottle. Some have the ability not only to remind a patient to take a medication, but also to text that patient’s caregiver (or parent, in the case of a teenager) if the medication is not taken.

While not perfect, these adherence apps are worth learning more about. They may be helpful additions to our efforts to achieve the best outcomes for our patients by helping them to actually take the medications that we so carefully prescribe.

References

1. Encinosa, W.E.; Bernard, D.; Dor, A. Does prescription drug adherence reduce hospitalizations and costs? The case of diabetes. Advances in Health Economics and Health Services Research 22, pp. 151-73, 2010 (AHRQ Publication No. 11-R008).

2. Am J Prev Med. 2015 Nov 17. pii: S0749-3797(15)00637-6. doi: 10.1016/j.amepre.2015.09.034.

Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia.

“Drugs don’t work in patients who don’t take them.”

–C. Everett Koop, M.D.

While it would be hard to imagine accountable care organizations being able to get the data they need to manage care without electronic health records, and EHRs are critical as payment has evolved to emphasize the outcomes of treatment, one area remains the holy grail of disease management: how to get patients to take the medications that are prescribed.

Poor adherence to medications is a critical issue in the management of chronic disease. The causes for suboptimal adherence are numerous, including the cost of medications, patient-physician communication, patient education, motivation, and simple forgetfulness.

Approximately 1.5 billion prescriptions, at a cost of more than $250 billion, are dispensed each year in the United States. A large body of evidence supports the use of these medications. For patients with diabetes, for instance, correct medication use can lower blood sugar, blood pressure, and cholesterol, and by so doing, decrease morbidity and mortality from both microvascular and macrovascular disease.

The act of taking medications is influenced by many factors, and all of these factors come together at a point in time when patients are not directly engaged with the health care system. It is at that moment that patients remember and decide whether to take their medications.

Numerous studies show that individuals often do not take their medicines as prescribed. Adherence rates for medications for chronic disease show that patients on average take only about 50% of prescribed doses. For patients with diabetes, the average adherence rate is about 70%, with rates ranging in different studies from 31% to 87%.

When patients do not take their medications correctly, there can be severe consequences. Poor medication adherence can lead to poorer clinical outcomes, including increased hospitalizations. One large dataset of more than 56,000 individuals with type 2 diabetes covered by employer-sponsored health insurance showed that increased adherence to medications significantly reduced hospitalizations and emergency department visits. When adherence rates increased, the hospitalization rate fell 23%, and the rate of emergency department visits decreased 46%, resulting in significant cost savings for the health system.¹

In response to this issue, many strategies have emerged. We now regularly get correspondence from insurance companies alerting us to nonadherence of individual patients. This information tends to be of little benefit, because the information is received long after the decision to take or not take the medication is made. Our response in the office to our patients is generally to remind them to take their medications, which is not much different from the discussion we have with them without that information.

Recently, a new set of apps for smartphones and tablets has emerged to help patients organize their approach to taking medications. Examples of some of these apps include Care4Today, Dosecast, Medisafe, MedSimple, MyMedREc, MyMeds, and OnTimeRx. Most of these apps allow a patient to put in their medication schedule and are organized to provide reminders when it is time to take medications.

The problem with reminders, of course, is that they don’t always happen at a time when it is convenient for a person to take their medications. For example, if your app reminds you to take your medicines at 9 p.m. each night, and you are at the movies on a Saturday night, you may extinguish the reminder and not remember to take the medications when you get home.

Many of the apps also track adherence rates so that patients can see how well they are doing in taking their medications. The results are often startling to patients, and it is hoped that such information would encourage more effort in taking medications.

One problem with many of the apps currently available is that they essentially function as sophisticated alarm clocks. They do not get at some of the fundamental reasons that people do not take their medications, which would require more behavioral input.

In fact, a recent article in the American Journal of Preventive Medicine looked at 166 medication adherence apps and concluded that current apps contained little in the way of evidence-based behavioral change techniques that have been shown to help change behavior. In fact, only about one-third of apps contained any feedback on behavior at all.²

While adherence apps still have a way to go, they can be helpful, and many contain interesting, novel features. Some allow the patient to input the name of a medication by scanning the name from the medication’s pill bottle. Some have the ability not only to remind a patient to take a medication, but also to text that patient’s caregiver (or parent, in the case of a teenager) if the medication is not taken.

While not perfect, these adherence apps are worth learning more about. They may be helpful additions to our efforts to achieve the best outcomes for our patients by helping them to actually take the medications that we so carefully prescribe.

References

1. Encinosa, W.E.; Bernard, D.; Dor, A. Does prescription drug adherence reduce hospitalizations and costs? The case of diabetes. Advances in Health Economics and Health Services Research 22, pp. 151-73, 2010 (AHRQ Publication No. 11-R008).

2. Am J Prev Med. 2015 Nov 17. pii: S0749-3797(15)00637-6. doi: 10.1016/j.amepre.2015.09.034.

Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia.

Editor’s Note: This is the fourth installment of a five-part monthly series that will discuss the biologic, genomic, and health system factors that contribute to the racial survival disparity in breast cancer. The series was adapted from an article that originally appeared in CA: A Cancer Journal for Clinicians,¹ a journal of the American Cancer Society. Eliminating racial disparities in cancer mortality through effective interventions has become an increasingly important imperative of federal, state, and community health care programs. This month’s column reviews interventions to close this survival gap.

Insurance

It has been posited that interventions aimed at providing insurance coverage to minority patients will be able to reduce racial health care disparities.² Studies have indicated that women without insurance present with more-advanced disease,^3,4 and are more likely to receive nonstandard treatment.⁵ However, outside of cancer care, a large study of Medicaid expansion in Oregon demonstrated that Medicaid coverage alone generated no significant improvement in measured physical health outcomes in the first 2 years.⁶ Thus, coverage alone does not ensure that patients will be able to navigate the health care system and that quality care will be provided.

In breast cancer, Hoffman et al.⁷ evaluated the effect of race and health insurance on diagnostic time, which was defined as the number of days from suspicious finding to diagnostic resolution (either no evidence of malignancy on diagnostic mammogram or definitive diagnosis by biopsy) in a large, urban setting. The authors’ hypothesis was that every insured patient would receive the same timely diagnosis as any other patient with equivalent insurance, regardless of race or ethnicity. The study found that non-Hispanic whites with government insurance had significantly shorter diagnostic times than did non-Hispanic African Americans with government insurance: The average diagnostic times were 12 and 39 days, respectively. In addition, privately insured non-Hispanic whites also had significantly shorter diagnostic times than did privately insured non-Hispanic African Americans (16 vs. 27 days). In addition, Short et al.⁸ demonstrated that when the health plan status was held constant in a retrospective study of 476 white patients and 99 African American patients with newly diagnosed breast cancer, African American patients had a higher mortality rate (8.1% vs. 3.6%) and were diagnosed at a later stage. Accordingly, interventions must go beyond just providing health insurance to minorities in order to have a significant impact on the mortality gap.

Patient education and physician communication

An underlying cause frequently cited for the delayed diagnosis and treatment of African American patients with breast cancer is a lack of patient education and physician communication. These elements are essential components of quality care. In a qualitative study of low-income, ethnically diverse women older than 40 years, Allen et al.⁹ identified salient themes differentiating women who received timely follow-up from those who did not. For the women who delayed follow-up, prominent themes were dissatisfaction with the communication of results, disrespect on the part of providers and clinical staff, logistical barriers to accessing services, anxiety and fear about a possible cancer diagnosis, and a lack of information about breast cancer screening and symptoms.

In another study, Masi and Gehlert¹⁰ employed focus group interviews of African American adults to characterize their perceptions of breast cancer treatment. The analysis revealed a core set of themes, including mistrust of the medical establishment and concern about the effect of racism on treatment quality; the researchers concluded that “in the eyes of many study participants, the issues of trust, race, and quality of care were closely intertwined.”¹⁰ Thus, this knot that is created by underlying issues of trust can be untied only by interventions that address improved physician communication and patient education.

Janz et al.¹¹ examined racial differences in the adequacy of information and support for women with breast cancer. The researchers used survey data from a population of 1,766 women diagnosed with nonmetastatic breast cancer and reported to the Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registry. The study found that across treatment- and survivorship-related issues, African American women desired more information than white women did. One of the explanations for the unmet information needs posited by the authors is a failure to provide culturally appropriate information related to health issues. This breakdown in patient education and communication was demonstrated by Hawley et al. to hold across providers and locations.¹²

Hawley et al.¹² evaluated the association between minority patients’ knowledge of breast cancer treatment risks and benefits and provider characteristics and treatment locations. The provider characteristics included surgeon-level independent variables, such as breast cancer procedure volume and demographics (years in practice and sex). The treatment location variable was categorized into one of three groups: National Cancer Institute–designated cancer center, American College of Surgeons cancer program, or no specific cancer program. Provider characteristics and treatment locations are factors previously identified as being associated with high-quality care.

The study employed a multivariable regression to identify associations between patient, surgeon, and treatment-setting factors and accurate knowledge of the survival benefit and recurrence risk related to mastectomy and breast-conserving surgery with radiation. The authors found that minority women were significantly less likely to have adequate knowledge and more likely to be uncertain about recurrence risk than were white patients. In the multivariate logistic regression model, neither provider characteristics nor treatment setting attenuated observed racial disparities in knowledge. Quality health care depends on the ability to make an informed treatment decision. As the authors concluded, this study underscores the need for providers to communicate information effectively to all patients, and effective communication relies on the cultural competency of providers.¹³ Without effective, culturally competent communication, there are treatment delays and omissions that result in poor-quality cancer care. Currently, the research has established that these communication deficits are found across providers and treatment center types.

Patient Navigation

Patient navigation has been championed as a method of improving care in breast cancer by enhancing patient communication and education, and removing barriers to timely care. Patient navigation empowers patients to become knowledgeable about their own health and supports them through the course of care.¹⁴ Patient navigation programs have been developed to address the patient communication breakdowns and underuse and misuse of treatment among vulnerable populations, which were detailed earlier in this series and are thought to contribute to the racial mortality gap.¹⁵

A benefit of patient navigation has been suggested in studies evaluating the time to diagnosis and follow-up from an abnormal screening. Markossian et al.¹⁶ evaluated the efficacy of a Chicago-based cancer patient navigation program developed to reduce the time from abnormal screening to definitive diagnostic testing. The majority of patients in this study were Hispanic (66%) and African American (32%). Compared with controls without navigation, the breast navigation group had a shorter time to diagnostic resolution. Hoffman et al.¹⁷ evaluated patient navigation in the District of Columbia to determine its ability to reduce the breast cancer diagnostic time (number of days from abnormal screening to a definitive diagnosis). African American women comprised 48% of the study population. The investigators found that women in the navigation group reached their diagnostic resolution significantly faster than did other women. Among women with breast cancer, there was a nearly fourfold reduction in time to diagnostic resolution for women in the navigation group versus women without a navigator.

In a national multicenter study, Ko et al.¹⁴ were the first to evaluate whether patient navigation can improve the quality of breast cancer care. The authors hypothesized that breast cancer patients assigned a navigator would be more likely to receive recommended standard treatment than were those without a navigator. Three separate quality measures of breast cancer care, including initiation of antiestrogen therapy, radiation therapy, and chemotherapy, were evaluated. Study participants were racially and ethnically diverse, with a plurality being African American (37.5%). The study produced mixed results: Patients in the navigation group had a statistically higher likelihood of receiving antiestrogen therapy than were non–navigated controls, but navigation patients eligible for radiation therapy were no more likely to receive it than were controls. The initiation of chemotherapy could not be accurately assessed because of a limited sample size. The study concluded that navigation alone does not remove all of the barriers to quality care for breast cancer patients, and barriers are diverse and potentially specific to the modality of treatment.

A study by Tejeda et al.¹⁸ used a systematic framework to characterize barriers faced by minority patients with breast and cervical cancer. The investigators categorized barriers as intrapersonal (defined by characteristics of the individual, such as knowledge, belief, attitudes, and transportation and financial barriers), interpersonal (defined by processes that involve other people, such as social support systems, child care, and employment issues), or institutional (defined by characteristics and policies of organizations). The authors found that although navigators were able to easily resolve intrapersonal barriers, ongoing navigation was needed to address institutional barriers. Thus, patient navigation in a vacuum does not work, and it is only in examining the entire health care system that changes can be implemented to eliminate barriers to quality care and close the racial mortality chasm.

System Change

To this effect, Clarke et al.¹⁹ performed a review of the disparities intervention literature to understand which interventions are being evaluated to improve minority health. The authors found that the majority of such interventions are focused on changing the patient rather than the system that serves her, with the most common strategy being education and training (37% of strategies studied). Interventions aimed at health care system improvements were surprisingly few, with the responsibility for change resting with the patient rather than the care delivery system. Interventions incorporating community involvement were also severely lacking and reflected only 6.5% of the reviewed intervention tactics. The majority of interventions failed to involve major stakeholders, including providers, health care institutions, community organizers, and policy makers, and accordingly, were unlikely to succeed in creating meaningful change.

In breast cancer, there have been examples of successful system-based approaches to reducing the racial mortality disparity. At New York area hospitals, Bickell et al.²⁰ implemented a tracking and feedback registry to close the referral loop between surgeons and oncologists to decrease the underuse of valuable adjuvant treatments.

The intervention targeted important quality issues in both communication (the breakdown in dialogue among providers of different specialties and between providers and patients) and the underuse of adjuvant treatment in minorities. The approach was designed to address failures in the health care system through the involvement of leadership from pathology, surgery, and oncology. The intervention also incorporated technology, with tracking software prompting contact with patients who had failed to follow up. Among African American and Hispanic women, there were statistically significant decreases in the underuse of radiotherapy (23% before the intervention vs. 10% after the intervention), chemotherapy (26% vs. 6%), and hormonal therapy (27% vs. 11%). After the intervention, minority race was no longer a risk factor for low rates of oncology consultation or underuse of adjuvant therapy. Interestingly, four of the six hospitals involved in this study had a patient navigation system in place; however, as discussed, the navigation system alone was not enough to address the system failures that led to disparities in care.

Ansell et al.²¹ also described a system-based approach to reducing the breast cancer mortality disparity in Chicago. The Metropolitan Chicago Breast Cancer Task Force comprised 102 individuals and 74 Chicago area organizations to address the growing disparity in breast cancer mortality between African American and white patients. The task force identified a number of themes underlying the disparity gap, including a need for breast cancer education and outreach programs for African American women, a broken mammography process leading to quality differences between African American and white patients, and a number of barriers to diagnosis and treatment, including fear, a lack of primary care, the burden of insurance copays/deductibles, and the noncompletion of treatment for social and economic reasons. After identifying these underlying causes, the task force proposed that addressing one aspect of the health care system would not correct the problem, but rather quality improvement initiatives would have to occur across the continuum of care for breast cancer.

In Delaware, such a broad system-based intervention was implemented to eliminate health disparities in colorectal cancer.²² Delaware created a comprehensive statewide colorectal screening and treatment program, combining many of the interventions discussed previously, including insurance coverage, patient education and communication, and patient navigation, to address the entire health care system and its treatment of African Americans with colorectal cancer. The state also partnered with underserved community organizations to tailor programs locally and create targeted marketing campaigns.

The results of this system-based approach were impressive, with screening rates among African American increasing from 48% to 74% and equaling the rate among whites. In addition, among African American patients, the percentage diagnosed at advanced and regional stages declined from 79% to 40%, and the percentage diagnosed at a local stage increased from 16% to 50%. Most importantly, the mortality rate declined by 42% for African Americans, resulting in a rate almost equal to that among whites. Significantly, this program was also found to be economically viable, because the cost savings from reduced cancer incidence and the stage shift to cancers requiring less-aggressive treatment offset the program cost. As the authors concluded, this model of a comprehensive, system-wide approach to the racial mortality difference would lend itself to other cancers, and more research is needed to assess and build such an approach to breast cancer.

As discussed in the aforementioned studies, multifaceted interventions that address all stakeholders are needed to close the racial survival disparity in breast cancer. In the final installment of this series, we will address how the changing care models ushered in by the Patient Protection and Affordable Care Act have the potential to advance this agenda of creating an intervention that works across the breast cancer care continuum to reduce disparities.

Other installments of this column can be found in the Related Content box.

1. Daly B, Olopade OI. A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change. CA Cancer J Clin. 2015 May-Jun;65(3):221-38.

2. Lillie-Blanton M, Hoffman C. The role of health insurance coverage in reducing racial/ethnic disparities in health care. Health Aff (Millwood). 2005 Mar-Apr;24(2):398-408.

3. Ayanian JZ, Kohler BA, Abe T, Epstein AM. The relation between health insurance coverage and clinical outcomes among women with breast cancer. N Engl J Med. 1993 Jul 29;329(5):326-31.

4. Coburn N, Fulton J, Pearlman DN, Law C, DiPaolo B, Cady B. Treatment variation by insurance status for breast cancer patients. Breast J. 2008 Mar-Apr;14(2):128-34.

5. Voti L, Richardson LC, Reis I, Fleming LE, Mackinnon J, Coebergh JW. The effect of race/ethnicity and insurance in the administration of standard therapy for local breast cancer in Florida. Breast Cancer Res Treat. 2006 Jan;95(1):89-95.

6. Baicker K, Taubman SL, Allen HL, et al. The Oregon experiment – effects of Medicaid on clinical outcomes. N Engl J Med. 2013 May 2;368(18):1713-22.

7. Hoffman HJ, LaVerda NL, Levine PH, et al. Having health insurance does not eliminate race/ethnicity-associated delays in breast cancer diagnosis in the District of Columbia. Cancer. 2011 Aug 15;117(16):3824-32.

8. Short LJ, Fisher MD, Wahl PM, et al. Disparities in medical care among commercially insured patients with newly diagnosed breast cancer: opportunities for intervention. Cancer. 2010 Jan 1;116(1):193-202.

9. Allen JD, Shelton RC, Harden E, Goldman RE. Follow-up of abnormal screening mammograms among low-income ethnically diverse women: findings from a qualitative study. Patient Educ Couns. 2008 Aug;72(2):283-92.

10. Masi CM, Gehlert S. Perceptions of breast cancer treatment among African-American women and men: implications for interventions. J Gen Intern Med. 2009 Mar;24(3):408-14.

11. Janz NK, Mujahid MS, Hawley ST, Griggs JJ, Hamilton AS, Katz SJ. Racial/ethnic differences in adequacy of information and support for women with breast cancer. Cancer. 2008 Sep 1;113(5):1058-67.

12. Hawley ST, Fagerlin A, Janz NK, Katz SJ. Racial/ethnic disparities in knowledge about risks and benefits of breast cancer treatment: does it matter where you go? Health Serv Res. 2008 Aug;43(4):1366-87.

13. Lannin DR, Mathews HF, Mitchell J, Swanson MS. Impacting cultural attitudes in African-American women to decrease breast cancer mortality. Am J Surg. 2002 Nov;184(5):418-23.

14. Ko NY, Darnell JS, Calhoun E, et al. Can patient navigation improve receipt of recommended breast cancer care? Evidence from the National Patient Navigation Research Program. J Clin Oncol. 2014 Sep 1;32(25):2758-64.

15. Vargas RB, Ryan GW, Jackson CA, Rodriguez R, Freeman HP. Characteristics of the original patient navigation programs to reduce disparities in the diagnosis and treatment of breast cancer. Cancer. 2008 Jul 15;113(2):426-33.

16. Markossian TW, Darnell JS, Calhoun EA. Follow-up and timeliness after an abnormal cancer screening among underserved, urban women in a patient navigation program. Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1691-700.

17. Hoffman HJ, LaVerda NL, Young HA, et al. Patient navigation significantly reduces delays in breast cancer diagnosis in the District of Columbia. Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1655-63.

18. Tejeda S, Darnell JS, Cho YI, Stolley MR, Markossian TW, Calhoun EA. Patient barriers to follow-up care for breast and cervical cancer abnormalities. J Womens Health (Larchmt). 2013 Jun;22(6):507-17.

19. Clarke AR, Goddu AP, Nocon RS, et al. Thirty years of disparities intervention research: what are we doing to close racial and ethnic gaps in health care? Med Care. 2013 Nov;51(11):1020-26.

20. Bickell NA, Shastri K, Fei K, et al. A tracking and feedback registry to reduce racial disparities in breast cancer care. J Natl Cancer Inst. 2008 Dec 3;100(23):1717-23.

21. Ansell D, Grabler P, Whitman S, et al. A community effort to reduce the black/white breast cancer mortality disparity in Chicago. Cancer Causes Control. 2009 Nov;20(9):1681-88.

22. Grubbs SS, Polite BN, Carney J, Jr., et al. Eliminating racial disparities in colorectal cancer in the real world: it took a village. J Clin Oncol. 2013 Jun 1;31(16):1928-30.

Olufunmilayo Olopade, MD, FACP, OON, is the Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, and director, Center for Global Health at the University of Chicago. She is adopting emerging high throughput genomic and informatics strategies to identify genetic and nongenetic risk factors for breast cancer in order to implement precision health care in diverse populations. This innovative approach has the potential to improve the quality of care and reduce costs while saving more lives.

Disclosures: Dr. Olopade serves on the Medical Advisory Board for CancerIQ. Dr. Daly serves as a director of Quadrant Holdings Corporation and receives compensation from this entity. Frontline Medical Communications is a subsidiary of Quadrant Holdings Corporation.

Published in conjunction with Susan G. Komen®.

Editor’s Note: This is the fourth installment of a five-part monthly series that will discuss the biologic, genomic, and health system factors that contribute to the racial survival disparity in breast cancer. The series was adapted from an article that originally appeared in CA: A Cancer Journal for Clinicians,¹ a journal of the American Cancer Society. Eliminating racial disparities in cancer mortality through effective interventions has become an increasingly important imperative of federal, state, and community health care programs. This month’s column reviews interventions to close this survival gap.

Insurance

It has been posited that interventions aimed at providing insurance coverage to minority patients will be able to reduce racial health care disparities.² Studies have indicated that women without insurance present with more-advanced disease,^3,4 and are more likely to receive nonstandard treatment.⁵ However, outside of cancer care, a large study of Medicaid expansion in Oregon demonstrated that Medicaid coverage alone generated no significant improvement in measured physical health outcomes in the first 2 years.⁶ Thus, coverage alone does not ensure that patients will be able to navigate the health care system and that quality care will be provided.

In breast cancer, Hoffman et al.⁷ evaluated the effect of race and health insurance on diagnostic time, which was defined as the number of days from suspicious finding to diagnostic resolution (either no evidence of malignancy on diagnostic mammogram or definitive diagnosis by biopsy) in a large, urban setting. The authors’ hypothesis was that every insured patient would receive the same timely diagnosis as any other patient with equivalent insurance, regardless of race or ethnicity. The study found that non-Hispanic whites with government insurance had significantly shorter diagnostic times than did non-Hispanic African Americans with government insurance: The average diagnostic times were 12 and 39 days, respectively. In addition, privately insured non-Hispanic whites also had significantly shorter diagnostic times than did privately insured non-Hispanic African Americans (16 vs. 27 days). In addition, Short et al.⁸ demonstrated that when the health plan status was held constant in a retrospective study of 476 white patients and 99 African American patients with newly diagnosed breast cancer, African American patients had a higher mortality rate (8.1% vs. 3.6%) and were diagnosed at a later stage. Accordingly, interventions must go beyond just providing health insurance to minorities in order to have a significant impact on the mortality gap.

Patient education and physician communication

An underlying cause frequently cited for the delayed diagnosis and treatment of African American patients with breast cancer is a lack of patient education and physician communication. These elements are essential components of quality care. In a qualitative study of low-income, ethnically diverse women older than 40 years, Allen et al.⁹ identified salient themes differentiating women who received timely follow-up from those who did not. For the women who delayed follow-up, prominent themes were dissatisfaction with the communication of results, disrespect on the part of providers and clinical staff, logistical barriers to accessing services, anxiety and fear about a possible cancer diagnosis, and a lack of information about breast cancer screening and symptoms.

In another study, Masi and Gehlert¹⁰ employed focus group interviews of African American adults to characterize their perceptions of breast cancer treatment. The analysis revealed a core set of themes, including mistrust of the medical establishment and concern about the effect of racism on treatment quality; the researchers concluded that “in the eyes of many study participants, the issues of trust, race, and quality of care were closely intertwined.”¹⁰ Thus, this knot that is created by underlying issues of trust can be untied only by interventions that address improved physician communication and patient education.

Janz et al.¹¹ examined racial differences in the adequacy of information and support for women with breast cancer. The researchers used survey data from a population of 1,766 women diagnosed with nonmetastatic breast cancer and reported to the Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registry. The study found that across treatment- and survivorship-related issues, African American women desired more information than white women did. One of the explanations for the unmet information needs posited by the authors is a failure to provide culturally appropriate information related to health issues. This breakdown in patient education and communication was demonstrated by Hawley et al. to hold across providers and locations.¹²

Hawley et al.¹² evaluated the association between minority patients’ knowledge of breast cancer treatment risks and benefits and provider characteristics and treatment locations. The provider characteristics included surgeon-level independent variables, such as breast cancer procedure volume and demographics (years in practice and sex). The treatment location variable was categorized into one of three groups: National Cancer Institute–designated cancer center, American College of Surgeons cancer program, or no specific cancer program. Provider characteristics and treatment locations are factors previously identified as being associated with high-quality care.

The study employed a multivariable regression to identify associations between patient, surgeon, and treatment-setting factors and accurate knowledge of the survival benefit and recurrence risk related to mastectomy and breast-conserving surgery with radiation. The authors found that minority women were significantly less likely to have adequate knowledge and more likely to be uncertain about recurrence risk than were white patients. In the multivariate logistic regression model, neither provider characteristics nor treatment setting attenuated observed racial disparities in knowledge. Quality health care depends on the ability to make an informed treatment decision. As the authors concluded, this study underscores the need for providers to communicate information effectively to all patients, and effective communication relies on the cultural competency of providers.¹³ Without effective, culturally competent communication, there are treatment delays and omissions that result in poor-quality cancer care. Currently, the research has established that these communication deficits are found across providers and treatment center types.

Patient Navigation

Patient navigation has been championed as a method of improving care in breast cancer by enhancing patient communication and education, and removing barriers to timely care. Patient navigation empowers patients to become knowledgeable about their own health and supports them through the course of care.¹⁴ Patient navigation programs have been developed to address the patient communication breakdowns and underuse and misuse of treatment among vulnerable populations, which were detailed earlier in this series and are thought to contribute to the racial mortality gap.¹⁵

A benefit of patient navigation has been suggested in studies evaluating the time to diagnosis and follow-up from an abnormal screening. Markossian et al.¹⁶ evaluated the efficacy of a Chicago-based cancer patient navigation program developed to reduce the time from abnormal screening to definitive diagnostic testing. The majority of patients in this study were Hispanic (66%) and African American (32%). Compared with controls without navigation, the breast navigation group had a shorter time to diagnostic resolution. Hoffman et al.¹⁷ evaluated patient navigation in the District of Columbia to determine its ability to reduce the breast cancer diagnostic time (number of days from abnormal screening to a definitive diagnosis). African American women comprised 48% of the study population. The investigators found that women in the navigation group reached their diagnostic resolution significantly faster than did other women. Among women with breast cancer, there was a nearly fourfold reduction in time to diagnostic resolution for women in the navigation group versus women without a navigator.

In a national multicenter study, Ko et al.¹⁴ were the first to evaluate whether patient navigation can improve the quality of breast cancer care. The authors hypothesized that breast cancer patients assigned a navigator would be more likely to receive recommended standard treatment than were those without a navigator. Three separate quality measures of breast cancer care, including initiation of antiestrogen therapy, radiation therapy, and chemotherapy, were evaluated. Study participants were racially and ethnically diverse, with a plurality being African American (37.5%). The study produced mixed results: Patients in the navigation group had a statistically higher likelihood of receiving antiestrogen therapy than were non–navigated controls, but navigation patients eligible for radiation therapy were no more likely to receive it than were controls. The initiation of chemotherapy could not be accurately assessed because of a limited sample size. The study concluded that navigation alone does not remove all of the barriers to quality care for breast cancer patients, and barriers are diverse and potentially specific to the modality of treatment.

A study by Tejeda et al.¹⁸ used a systematic framework to characterize barriers faced by minority patients with breast and cervical cancer. The investigators categorized barriers as intrapersonal (defined by characteristics of the individual, such as knowledge, belief, attitudes, and transportation and financial barriers), interpersonal (defined by processes that involve other people, such as social support systems, child care, and employment issues), or institutional (defined by characteristics and policies of organizations). The authors found that although navigators were able to easily resolve intrapersonal barriers, ongoing navigation was needed to address institutional barriers. Thus, patient navigation in a vacuum does not work, and it is only in examining the entire health care system that changes can be implemented to eliminate barriers to quality care and close the racial mortality chasm.

System Change

To this effect, Clarke et al.¹⁹ performed a review of the disparities intervention literature to understand which interventions are being evaluated to improve minority health. The authors found that the majority of such interventions are focused on changing the patient rather than the system that serves her, with the most common strategy being education and training (37% of strategies studied). Interventions aimed at health care system improvements were surprisingly few, with the responsibility for change resting with the patient rather than the care delivery system. Interventions incorporating community involvement were also severely lacking and reflected only 6.5% of the reviewed intervention tactics. The majority of interventions failed to involve major stakeholders, including providers, health care institutions, community organizers, and policy makers, and accordingly, were unlikely to succeed in creating meaningful change.

In breast cancer, there have been examples of successful system-based approaches to reducing the racial mortality disparity. At New York area hospitals, Bickell et al.²⁰ implemented a tracking and feedback registry to close the referral loop between surgeons and oncologists to decrease the underuse of valuable adjuvant treatments.

The intervention targeted important quality issues in both communication (the breakdown in dialogue among providers of different specialties and between providers and patients) and the underuse of adjuvant treatment in minorities. The approach was designed to address failures in the health care system through the involvement of leadership from pathology, surgery, and oncology. The intervention also incorporated technology, with tracking software prompting contact with patients who had failed to follow up. Among African American and Hispanic women, there were statistically significant decreases in the underuse of radiotherapy (23% before the intervention vs. 10% after the intervention), chemotherapy (26% vs. 6%), and hormonal therapy (27% vs. 11%). After the intervention, minority race was no longer a risk factor for low rates of oncology consultation or underuse of adjuvant therapy. Interestingly, four of the six hospitals involved in this study had a patient navigation system in place; however, as discussed, the navigation system alone was not enough to address the system failures that led to disparities in care.

Ansell et al.²¹ also described a system-based approach to reducing the breast cancer mortality disparity in Chicago. The Metropolitan Chicago Breast Cancer Task Force comprised 102 individuals and 74 Chicago area organizations to address the growing disparity in breast cancer mortality between African American and white patients. The task force identified a number of themes underlying the disparity gap, including a need for breast cancer education and outreach programs for African American women, a broken mammography process leading to quality differences between African American and white patients, and a number of barriers to diagnosis and treatment, including fear, a lack of primary care, the burden of insurance copays/deductibles, and the noncompletion of treatment for social and economic reasons. After identifying these underlying causes, the task force proposed that addressing one aspect of the health care system would not correct the problem, but rather quality improvement initiatives would have to occur across the continuum of care for breast cancer.

In Delaware, such a broad system-based intervention was implemented to eliminate health disparities in colorectal cancer.²² Delaware created a comprehensive statewide colorectal screening and treatment program, combining many of the interventions discussed previously, including insurance coverage, patient education and communication, and patient navigation, to address the entire health care system and its treatment of African Americans with colorectal cancer. The state also partnered with underserved community organizations to tailor programs locally and create targeted marketing campaigns.

The results of this system-based approach were impressive, with screening rates among African American increasing from 48% to 74% and equaling the rate among whites. In addition, among African American patients, the percentage diagnosed at advanced and regional stages declined from 79% to 40%, and the percentage diagnosed at a local stage increased from 16% to 50%. Most importantly, the mortality rate declined by 42% for African Americans, resulting in a rate almost equal to that among whites. Significantly, this program was also found to be economically viable, because the cost savings from reduced cancer incidence and the stage shift to cancers requiring less-aggressive treatment offset the program cost. As the authors concluded, this model of a comprehensive, system-wide approach to the racial mortality difference would lend itself to other cancers, and more research is needed to assess and build such an approach to breast cancer.

As discussed in the aforementioned studies, multifaceted interventions that address all stakeholders are needed to close the racial survival disparity in breast cancer. In the final installment of this series, we will address how the changing care models ushered in by the Patient Protection and Affordable Care Act have the potential to advance this agenda of creating an intervention that works across the breast cancer care continuum to reduce disparities.

Other installments of this column can be found in the Related Content box.

1. Daly B, Olopade OI. A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change. CA Cancer J Clin. 2015 May-Jun;65(3):221-38.

2. Lillie-Blanton M, Hoffman C. The role of health insurance coverage in reducing racial/ethnic disparities in health care. Health Aff (Millwood). 2005 Mar-Apr;24(2):398-408.

3. Ayanian JZ, Kohler BA, Abe T, Epstein AM. The relation between health insurance coverage and clinical outcomes among women with breast cancer. N Engl J Med. 1993 Jul 29;329(5):326-31.

4. Coburn N, Fulton J, Pearlman DN, Law C, DiPaolo B, Cady B. Treatment variation by insurance status for breast cancer patients. Breast J. 2008 Mar-Apr;14(2):128-34.

5. Voti L, Richardson LC, Reis I, Fleming LE, Mackinnon J, Coebergh JW. The effect of race/ethnicity and insurance in the administration of standard therapy for local breast cancer in Florida. Breast Cancer Res Treat. 2006 Jan;95(1):89-95.

6. Baicker K, Taubman SL, Allen HL, et al. The Oregon experiment – effects of Medicaid on clinical outcomes. N Engl J Med. 2013 May 2;368(18):1713-22.

7. Hoffman HJ, LaVerda NL, Levine PH, et al. Having health insurance does not eliminate race/ethnicity-associated delays in breast cancer diagnosis in the District of Columbia. Cancer. 2011 Aug 15;117(16):3824-32.

8. Short LJ, Fisher MD, Wahl PM, et al. Disparities in medical care among commercially insured patients with newly diagnosed breast cancer: opportunities for intervention. Cancer. 2010 Jan 1;116(1):193-202.

9. Allen JD, Shelton RC, Harden E, Goldman RE. Follow-up of abnormal screening mammograms among low-income ethnically diverse women: findings from a qualitative study. Patient Educ Couns. 2008 Aug;72(2):283-92.

10. Masi CM, Gehlert S. Perceptions of breast cancer treatment among African-American women and men: implications for interventions. J Gen Intern Med. 2009 Mar;24(3):408-14.

11. Janz NK, Mujahid MS, Hawley ST, Griggs JJ, Hamilton AS, Katz SJ. Racial/ethnic differences in adequacy of information and support for women with breast cancer. Cancer. 2008 Sep 1;113(5):1058-67.

12. Hawley ST, Fagerlin A, Janz NK, Katz SJ. Racial/ethnic disparities in knowledge about risks and benefits of breast cancer treatment: does it matter where you go? Health Serv Res. 2008 Aug;43(4):1366-87.

13. Lannin DR, Mathews HF, Mitchell J, Swanson MS. Impacting cultural attitudes in African-American women to decrease breast cancer mortality. Am J Surg. 2002 Nov;184(5):418-23.

14. Ko NY, Darnell JS, Calhoun E, et al. Can patient navigation improve receipt of recommended breast cancer care? Evidence from the National Patient Navigation Research Program. J Clin Oncol. 2014 Sep 1;32(25):2758-64.

15. Vargas RB, Ryan GW, Jackson CA, Rodriguez R, Freeman HP. Characteristics of the original patient navigation programs to reduce disparities in the diagnosis and treatment of breast cancer. Cancer. 2008 Jul 15;113(2):426-33.

16. Markossian TW, Darnell JS, Calhoun EA. Follow-up and timeliness after an abnormal cancer screening among underserved, urban women in a patient navigation program. Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1691-700.

17. Hoffman HJ, LaVerda NL, Young HA, et al. Patient navigation significantly reduces delays in breast cancer diagnosis in the District of Columbia. Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1655-63.

18. Tejeda S, Darnell JS, Cho YI, Stolley MR, Markossian TW, Calhoun EA. Patient barriers to follow-up care for breast and cervical cancer abnormalities. J Womens Health (Larchmt). 2013 Jun;22(6):507-17.

19. Clarke AR, Goddu AP, Nocon RS, et al. Thirty years of disparities intervention research: what are we doing to close racial and ethnic gaps in health care? Med Care. 2013 Nov;51(11):1020-26.

20. Bickell NA, Shastri K, Fei K, et al. A tracking and feedback registry to reduce racial disparities in breast cancer care. J Natl Cancer Inst. 2008 Dec 3;100(23):1717-23.

21. Ansell D, Grabler P, Whitman S, et al. A community effort to reduce the black/white breast cancer mortality disparity in Chicago. Cancer Causes Control. 2009 Nov;20(9):1681-88.

22. Grubbs SS, Polite BN, Carney J, Jr., et al. Eliminating racial disparities in colorectal cancer in the real world: it took a village. J Clin Oncol. 2013 Jun 1;31(16):1928-30.

Olufunmilayo Olopade, MD, FACP, OON, is the Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, and director, Center for Global Health at the University of Chicago. She is adopting emerging high throughput genomic and informatics strategies to identify genetic and nongenetic risk factors for breast cancer in order to implement precision health care in diverse populations. This innovative approach has the potential to improve the quality of care and reduce costs while saving more lives.

Disclosures: Dr. Olopade serves on the Medical Advisory Board for CancerIQ. Dr. Daly serves as a director of Quadrant Holdings Corporation and receives compensation from this entity. Frontline Medical Communications is a subsidiary of Quadrant Holdings Corporation.

Published in conjunction with Susan G. Komen®.

Editor’s Note: This is the fourth installment of a five-part monthly series that will discuss the biologic, genomic, and health system factors that contribute to the racial survival disparity in breast cancer. The series was adapted from an article that originally appeared in CA: A Cancer Journal for Clinicians,¹ a journal of the American Cancer Society. Eliminating racial disparities in cancer mortality through effective interventions has become an increasingly important imperative of federal, state, and community health care programs. This month’s column reviews interventions to close this survival gap.

Insurance

It has been posited that interventions aimed at providing insurance coverage to minority patients will be able to reduce racial health care disparities.² Studies have indicated that women without insurance present with more-advanced disease,^3,4 and are more likely to receive nonstandard treatment.⁵ However, outside of cancer care, a large study of Medicaid expansion in Oregon demonstrated that Medicaid coverage alone generated no significant improvement in measured physical health outcomes in the first 2 years.⁶ Thus, coverage alone does not ensure that patients will be able to navigate the health care system and that quality care will be provided.

In breast cancer, Hoffman et al.⁷ evaluated the effect of race and health insurance on diagnostic time, which was defined as the number of days from suspicious finding to diagnostic resolution (either no evidence of malignancy on diagnostic mammogram or definitive diagnosis by biopsy) in a large, urban setting. The authors’ hypothesis was that every insured patient would receive the same timely diagnosis as any other patient with equivalent insurance, regardless of race or ethnicity. The study found that non-Hispanic whites with government insurance had significantly shorter diagnostic times than did non-Hispanic African Americans with government insurance: The average diagnostic times were 12 and 39 days, respectively. In addition, privately insured non-Hispanic whites also had significantly shorter diagnostic times than did privately insured non-Hispanic African Americans (16 vs. 27 days). In addition, Short et al.⁸ demonstrated that when the health plan status was held constant in a retrospective study of 476 white patients and 99 African American patients with newly diagnosed breast cancer, African American patients had a higher mortality rate (8.1% vs. 3.6%) and were diagnosed at a later stage. Accordingly, interventions must go beyond just providing health insurance to minorities in order to have a significant impact on the mortality gap.

Patient education and physician communication

An underlying cause frequently cited for the delayed diagnosis and treatment of African American patients with breast cancer is a lack of patient education and physician communication. These elements are essential components of quality care. In a qualitative study of low-income, ethnically diverse women older than 40 years, Allen et al.⁹ identified salient themes differentiating women who received timely follow-up from those who did not. For the women who delayed follow-up, prominent themes were dissatisfaction with the communication of results, disrespect on the part of providers and clinical staff, logistical barriers to accessing services, anxiety and fear about a possible cancer diagnosis, and a lack of information about breast cancer screening and symptoms.

In another study, Masi and Gehlert¹⁰ employed focus group interviews of African American adults to characterize their perceptions of breast cancer treatment. The analysis revealed a core set of themes, including mistrust of the medical establishment and concern about the effect of racism on treatment quality; the researchers concluded that “in the eyes of many study participants, the issues of trust, race, and quality of care were closely intertwined.”¹⁰ Thus, this knot that is created by underlying issues of trust can be untied only by interventions that address improved physician communication and patient education.

Janz et al.¹¹ examined racial differences in the adequacy of information and support for women with breast cancer. The researchers used survey data from a population of 1,766 women diagnosed with nonmetastatic breast cancer and reported to the Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registry. The study found that across treatment- and survivorship-related issues, African American women desired more information than white women did. One of the explanations for the unmet information needs posited by the authors is a failure to provide culturally appropriate information related to health issues. This breakdown in patient education and communication was demonstrated by Hawley et al. to hold across providers and locations.¹²

Hawley et al.¹² evaluated the association between minority patients’ knowledge of breast cancer treatment risks and benefits and provider characteristics and treatment locations. The provider characteristics included surgeon-level independent variables, such as breast cancer procedure volume and demographics (years in practice and sex). The treatment location variable was categorized into one of three groups: National Cancer Institute–designated cancer center, American College of Surgeons cancer program, or no specific cancer program. Provider characteristics and treatment locations are factors previously identified as being associated with high-quality care.

The study employed a multivariable regression to identify associations between patient, surgeon, and treatment-setting factors and accurate knowledge of the survival benefit and recurrence risk related to mastectomy and breast-conserving surgery with radiation. The authors found that minority women were significantly less likely to have adequate knowledge and more likely to be uncertain about recurrence risk than were white patients. In the multivariate logistic regression model, neither provider characteristics nor treatment setting attenuated observed racial disparities in knowledge. Quality health care depends on the ability to make an informed treatment decision. As the authors concluded, this study underscores the need for providers to communicate information effectively to all patients, and effective communication relies on the cultural competency of providers.¹³ Without effective, culturally competent communication, there are treatment delays and omissions that result in poor-quality cancer care. Currently, the research has established that these communication deficits are found across providers and treatment center types.

Patient Navigation

Patient navigation has been championed as a method of improving care in breast cancer by enhancing patient communication and education, and removing barriers to timely care. Patient navigation empowers patients to become knowledgeable about their own health and supports them through the course of care.¹⁴ Patient navigation programs have been developed to address the patient communication breakdowns and underuse and misuse of treatment among vulnerable populations, which were detailed earlier in this series and are thought to contribute to the racial mortality gap.¹⁵

A benefit of patient navigation has been suggested in studies evaluating the time to diagnosis and follow-up from an abnormal screening. Markossian et al.¹⁶ evaluated the efficacy of a Chicago-based cancer patient navigation program developed to reduce the time from abnormal screening to definitive diagnostic testing. The majority of patients in this study were Hispanic (66%) and African American (32%). Compared with controls without navigation, the breast navigation group had a shorter time to diagnostic resolution. Hoffman et al.¹⁷ evaluated patient navigation in the District of Columbia to determine its ability to reduce the breast cancer diagnostic time (number of days from abnormal screening to a definitive diagnosis). African American women comprised 48% of the study population. The investigators found that women in the navigation group reached their diagnostic resolution significantly faster than did other women. Among women with breast cancer, there was a nearly fourfold reduction in time to diagnostic resolution for women in the navigation group versus women without a navigator.

In a national multicenter study, Ko et al.¹⁴ were the first to evaluate whether patient navigation can improve the quality of breast cancer care. The authors hypothesized that breast cancer patients assigned a navigator would be more likely to receive recommended standard treatment than were those without a navigator. Three separate quality measures of breast cancer care, including initiation of antiestrogen therapy, radiation therapy, and chemotherapy, were evaluated. Study participants were racially and ethnically diverse, with a plurality being African American (37.5%). The study produced mixed results: Patients in the navigation group had a statistically higher likelihood of receiving antiestrogen therapy than were non–navigated controls, but navigation patients eligible for radiation therapy were no more likely to receive it than were controls. The initiation of chemotherapy could not be accurately assessed because of a limited sample size. The study concluded that navigation alone does not remove all of the barriers to quality care for breast cancer patients, and barriers are diverse and potentially specific to the modality of treatment.

A study by Tejeda et al.¹⁸ used a systematic framework to characterize barriers faced by minority patients with breast and cervical cancer. The investigators categorized barriers as intrapersonal (defined by characteristics of the individual, such as knowledge, belief, attitudes, and transportation and financial barriers), interpersonal (defined by processes that involve other people, such as social support systems, child care, and employment issues), or institutional (defined by characteristics and policies of organizations). The authors found that although navigators were able to easily resolve intrapersonal barriers, ongoing navigation was needed to address institutional barriers. Thus, patient navigation in a vacuum does not work, and it is only in examining the entire health care system that changes can be implemented to eliminate barriers to quality care and close the racial mortality chasm.

System Change

To this effect, Clarke et al.¹⁹ performed a review of the disparities intervention literature to understand which interventions are being evaluated to improve minority health. The authors found that the majority of such interventions are focused on changing the patient rather than the system that serves her, with the most common strategy being education and training (37% of strategies studied). Interventions aimed at health care system improvements were surprisingly few, with the responsibility for change resting with the patient rather than the care delivery system. Interventions incorporating community involvement were also severely lacking and reflected only 6.5% of the reviewed intervention tactics. The majority of interventions failed to involve major stakeholders, including providers, health care institutions, community organizers, and policy makers, and accordingly, were unlikely to succeed in creating meaningful change.

In breast cancer, there have been examples of successful system-based approaches to reducing the racial mortality disparity. At New York area hospitals, Bickell et al.²⁰ implemented a tracking and feedback registry to close the referral loop between surgeons and oncologists to decrease the underuse of valuable adjuvant treatments.

The intervention targeted important quality issues in both communication (the breakdown in dialogue among providers of different specialties and between providers and patients) and the underuse of adjuvant treatment in minorities. The approach was designed to address failures in the health care system through the involvement of leadership from pathology, surgery, and oncology. The intervention also incorporated technology, with tracking software prompting contact with patients who had failed to follow up. Among African American and Hispanic women, there were statistically significant decreases in the underuse of radiotherapy (23% before the intervention vs. 10% after the intervention), chemotherapy (26% vs. 6%), and hormonal therapy (27% vs. 11%). After the intervention, minority race was no longer a risk factor for low rates of oncology consultation or underuse of adjuvant therapy. Interestingly, four of the six hospitals involved in this study had a patient navigation system in place; however, as discussed, the navigation system alone was not enough to address the system failures that led to disparities in care.

Ansell et al.²¹ also described a system-based approach to reducing the breast cancer mortality disparity in Chicago. The Metropolitan Chicago Breast Cancer Task Force comprised 102 individuals and 74 Chicago area organizations to address the growing disparity in breast cancer mortality between African American and white patients. The task force identified a number of themes underlying the disparity gap, including a need for breast cancer education and outreach programs for African American women, a broken mammography process leading to quality differences between African American and white patients, and a number of barriers to diagnosis and treatment, including fear, a lack of primary care, the burden of insurance copays/deductibles, and the noncompletion of treatment for social and economic reasons. After identifying these underlying causes, the task force proposed that addressing one aspect of the health care system would not correct the problem, but rather quality improvement initiatives would have to occur across the continuum of care for breast cancer.

In Delaware, such a broad system-based intervention was implemented to eliminate health disparities in colorectal cancer.²² Delaware created a comprehensive statewide colorectal screening and treatment program, combining many of the interventions discussed previously, including insurance coverage, patient education and communication, and patient navigation, to address the entire health care system and its treatment of African Americans with colorectal cancer. The state also partnered with underserved community organizations to tailor programs locally and create targeted marketing campaigns.

The results of this system-based approach were impressive, with screening rates among African American increasing from 48% to 74% and equaling the rate among whites. In addition, among African American patients, the percentage diagnosed at advanced and regional stages declined from 79% to 40%, and the percentage diagnosed at a local stage increased from 16% to 50%. Most importantly, the mortality rate declined by 42% for African Americans, resulting in a rate almost equal to that among whites. Significantly, this program was also found to be economically viable, because the cost savings from reduced cancer incidence and the stage shift to cancers requiring less-aggressive treatment offset the program cost. As the authors concluded, this model of a comprehensive, system-wide approach to the racial mortality difference would lend itself to other cancers, and more research is needed to assess and build such an approach to breast cancer.

As discussed in the aforementioned studies, multifaceted interventions that address all stakeholders are needed to close the racial survival disparity in breast cancer. In the final installment of this series, we will address how the changing care models ushered in by the Patient Protection and Affordable Care Act have the potential to advance this agenda of creating an intervention that works across the breast cancer care continuum to reduce disparities.

Other installments of this column can be found in the Related Content box.

1. Daly B, Olopade OI. A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change. CA Cancer J Clin. 2015 May-Jun;65(3):221-38.

2. Lillie-Blanton M, Hoffman C. The role of health insurance coverage in reducing racial/ethnic disparities in health care. Health Aff (Millwood). 2005 Mar-Apr;24(2):398-408.

3. Ayanian JZ, Kohler BA, Abe T, Epstein AM. The relation between health insurance coverage and clinical outcomes among women with breast cancer. N Engl J Med. 1993 Jul 29;329(5):326-31.

4. Coburn N, Fulton J, Pearlman DN, Law C, DiPaolo B, Cady B. Treatment variation by insurance status for breast cancer patients. Breast J. 2008 Mar-Apr;14(2):128-34.

5. Voti L, Richardson LC, Reis I, Fleming LE, Mackinnon J, Coebergh JW. The effect of race/ethnicity and insurance in the administration of standard therapy for local breast cancer in Florida. Breast Cancer Res Treat. 2006 Jan;95(1):89-95.

6. Baicker K, Taubman SL, Allen HL, et al. The Oregon experiment – effects of Medicaid on clinical outcomes. N Engl J Med. 2013 May 2;368(18):1713-22.

7. Hoffman HJ, LaVerda NL, Levine PH, et al. Having health insurance does not eliminate race/ethnicity-associated delays in breast cancer diagnosis in the District of Columbia. Cancer. 2011 Aug 15;117(16):3824-32.

8. Short LJ, Fisher MD, Wahl PM, et al. Disparities in medical care among commercially insured patients with newly diagnosed breast cancer: opportunities for intervention. Cancer. 2010 Jan 1;116(1):193-202.

9. Allen JD, Shelton RC, Harden E, Goldman RE. Follow-up of abnormal screening mammograms among low-income ethnically diverse women: findings from a qualitative study. Patient Educ Couns. 2008 Aug;72(2):283-92.

10. Masi CM, Gehlert S. Perceptions of breast cancer treatment among African-American women and men: implications for interventions. J Gen Intern Med. 2009 Mar;24(3):408-14.

11. Janz NK, Mujahid MS, Hawley ST, Griggs JJ, Hamilton AS, Katz SJ. Racial/ethnic differences in adequacy of information and support for women with breast cancer. Cancer. 2008 Sep 1;113(5):1058-67.

12. Hawley ST, Fagerlin A, Janz NK, Katz SJ. Racial/ethnic disparities in knowledge about risks and benefits of breast cancer treatment: does it matter where you go? Health Serv Res. 2008 Aug;43(4):1366-87.

13. Lannin DR, Mathews HF, Mitchell J, Swanson MS. Impacting cultural attitudes in African-American women to decrease breast cancer mortality. Am J Surg. 2002 Nov;184(5):418-23.

14. Ko NY, Darnell JS, Calhoun E, et al. Can patient navigation improve receipt of recommended breast cancer care? Evidence from the National Patient Navigation Research Program. J Clin Oncol. 2014 Sep 1;32(25):2758-64.

15. Vargas RB, Ryan GW, Jackson CA, Rodriguez R, Freeman HP. Characteristics of the original patient navigation programs to reduce disparities in the diagnosis and treatment of breast cancer. Cancer. 2008 Jul 15;113(2):426-33.

16. Markossian TW, Darnell JS, Calhoun EA. Follow-up and timeliness after an abnormal cancer screening among underserved, urban women in a patient navigation program. Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1691-700.

17. Hoffman HJ, LaVerda NL, Young HA, et al. Patient navigation significantly reduces delays in breast cancer diagnosis in the District of Columbia. Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1655-63.

18. Tejeda S, Darnell JS, Cho YI, Stolley MR, Markossian TW, Calhoun EA. Patient barriers to follow-up care for breast and cervical cancer abnormalities. J Womens Health (Larchmt). 2013 Jun;22(6):507-17.

19. Clarke AR, Goddu AP, Nocon RS, et al. Thirty years of disparities intervention research: what are we doing to close racial and ethnic gaps in health care? Med Care. 2013 Nov;51(11):1020-26.

20. Bickell NA, Shastri K, Fei K, et al. A tracking and feedback registry to reduce racial disparities in breast cancer care. J Natl Cancer Inst. 2008 Dec 3;100(23):1717-23.

21. Ansell D, Grabler P, Whitman S, et al. A community effort to reduce the black/white breast cancer mortality disparity in Chicago. Cancer Causes Control. 2009 Nov;20(9):1681-88.

22. Grubbs SS, Polite BN, Carney J, Jr., et al. Eliminating racial disparities in colorectal cancer in the real world: it took a village. J Clin Oncol. 2013 Jun 1;31(16):1928-30.

Olufunmilayo Olopade, MD, FACP, OON, is the Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, and director, Center for Global Health at the University of Chicago. She is adopting emerging high throughput genomic and informatics strategies to identify genetic and nongenetic risk factors for breast cancer in order to implement precision health care in diverse populations. This innovative approach has the potential to improve the quality of care and reduce costs while saving more lives.

Disclosures: Dr. Olopade serves on the Medical Advisory Board for CancerIQ. Dr. Daly serves as a director of Quadrant Holdings Corporation and receives compensation from this entity. Frontline Medical Communications is a subsidiary of Quadrant Holdings Corporation.

Published in conjunction with Susan G. Komen®.

“CAN WE SOLVE THE PROBLEM OF INADEQUATE CONTRACEPTION FOR WOMEN AT HIGH RISK FOR ADVERSE PREGNANCY OUTCOMES?”
ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2016)

“Contraception as a vital sign”
In his recent Editorial Dr. Barbieri asked for ideas to improve contraception counseling for women with medical problems that put them at risk for adverse pregnancy outcomes. His idea of “contraception status as a vital sign” is applied in our very large group practice in Northern California using the electronic health record (EHR).

Over 10 years ago, I attempted to put a hard stop in the EHR to require documentation that women of reproductive age be evaluated for contraception. This scheme seemed to be too cumbersome and was rejected at the time.

The idea was not abandoned, however. Medical assistants must now document a means of contraception for each woman of reproductive age. This does not guarantee that a physician will look at the information, but it is a step in the right direction.

My hope is that someday we will have automatic contraception as a vital sign documentation for all reproductive-age women, including “children” who are documented as menstruating. In the meantime, thank you for highlighting this critical issue.

Tia Will, MD
Sacramento, California

Reduce reimbursement when standard of care is not met
When I read Dr. Barbieri’s Editorial, I was surprised that he avoided the elephant in the room: the current political climate of denying contraception to women, including the defunding of Planned Parenthood and the Supreme Court decision to allow corporations to deny contraceptive coverage for religious issues.

Although I am not currently involved in women’s health, I do work under the auspices of a large Catholic health care system in the United States. Here, all employees are prohibited from providing contraceptive procedures, prescriptions, or even counseling unless it is a Natural Family Planning/ Fertility Awareness Method. These employees also are not provided individual contraceptive health coverage by their employer; this coverage is provided by the federal government thanks to the Affordable Care Act.

Contraception is part of the standard of care for women. However, many women are denied this standard of care due to “religious” reasons, which I suspect may be partially financial and/or political in nature. 

This issue must therefore be addressed by political and financial means. My recommendation is for legislation that mandates lower reimbursement rates for health care systems and providers that refuse to offer full contraceptive options to women. If they do not provide full care, they do not get full payment for services. The money saved by reduced reimbursements could then fund federal women’s health clinics in areas dominated by “religious” health care systems that would guarantee full reproductive health options to all.

Name and practice location withheld

Remove Medicaid barriers to postpartum sterilization
An issue not addressed in Dr. Barbieri’s Editorial is that of women who, after appropriate and extensive counseling by a physician and with a full understanding of the reproductive implications and the possible adverse effect of additional pregnancies on their health and life, decide for permanent contraception. A woman’s opportunity to obtain postpartum or interval contraceptive procedure varies by her insurance coverage, which is indirectly associated with her ethnicity or race.

In 1979, Medicaid Title XIX imposed a 30-day interval between the signing of the sterilization informed consent by the patient and the performance of the procedure. These regulations are still in effect today. What was instituted to protect vulnerable populations from coerced methods in the 1970s represents an anachronistic and archaic approach in the 21st Century. This regulation discriminates against low-income and minority women whose health care is covered by public insurance yet who are frequently at highest risk for unintended and possible risky pregnancy or abortion. In simple words, this imposition violates the standards of justice, beneficence, and nonmaleficence as it treats publicly insured women differently from privately insured women.

The American Medical Association and the American College of Obstetricians and Gynecologists¹ state that this regulation must be revised and charged practitioners to develop policies and procedures to ensure all women who desire postpartum sterilization can receive it. It is incumbent upon all women’s health care physicians to see that this barrier is removed.

Federico G. Mariona, MD, MHSA
Dearborn, Michigan

Reference

Educate the sexual partners of at-risk women
It always strikes me how little emphasis is placed on including the sexual partners of women with serious medical problems in the dialogue about responsibility for at-risk pregnancy. As advocates for women’s health, we should educate the couple about vasectomy and liberally provide referrals. Community outreach to help men understand how they can protect their partner from potentially dangerous unwanted pregnancy is extremely important and not stressed enough. Vasectomy is a quick, safe procedure performed in a physician’s office under local anesthesia. Why should any woman who has already risked her life carrying and delivering a baby be required to bear the contraceptive burden when there is a safe and convenient alternative?

Emily Gubert, MD
East Islip, New York

Dr. Barbieri responds
I thank Drs. Will, Mariona, and Gubert and the anonymous author for their wonderful recommendations on approaches to help improve contraceptive care for women. I agree with Dr. Will that the EHR is a valuable tool to advance contraceptive care. The anonymous author and Dr. Mariona make the critically important point that all women should have access to desired contraception without any barriers based on institutional beliefs or government regulations. The patient’s needs should be prioritized in all medical decision making. I agree with Dr. Gubert that including the male partner in the care process is an important part of effective contraception for women. I enthusiastically agree with her that the best permanent contraceptive for a stable couple is vasectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“CAN WE SOLVE THE PROBLEM OF INADEQUATE CONTRACEPTION FOR WOMEN AT HIGH RISK FOR ADVERSE PREGNANCY OUTCOMES?”
ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2016)

“Contraception as a vital sign”
In his recent Editorial Dr. Barbieri asked for ideas to improve contraception counseling for women with medical problems that put them at risk for adverse pregnancy outcomes. His idea of “contraception status as a vital sign” is applied in our very large group practice in Northern California using the electronic health record (EHR).

Over 10 years ago, I attempted to put a hard stop in the EHR to require documentation that women of reproductive age be evaluated for contraception. This scheme seemed to be too cumbersome and was rejected at the time.

The idea was not abandoned, however. Medical assistants must now document a means of contraception for each woman of reproductive age. This does not guarantee that a physician will look at the information, but it is a step in the right direction.

My hope is that someday we will have automatic contraception as a vital sign documentation for all reproductive-age women, including “children” who are documented as menstruating. In the meantime, thank you for highlighting this critical issue.

Tia Will, MD
Sacramento, California

Reduce reimbursement when standard of care is not met
When I read Dr. Barbieri’s Editorial, I was surprised that he avoided the elephant in the room: the current political climate of denying contraception to women, including the defunding of Planned Parenthood and the Supreme Court decision to allow corporations to deny contraceptive coverage for religious issues.

Although I am not currently involved in women’s health, I do work under the auspices of a large Catholic health care system in the United States. Here, all employees are prohibited from providing contraceptive procedures, prescriptions, or even counseling unless it is a Natural Family Planning/ Fertility Awareness Method. These employees also are not provided individual contraceptive health coverage by their employer; this coverage is provided by the federal government thanks to the Affordable Care Act.

Contraception is part of the standard of care for women. However, many women are denied this standard of care due to “religious” reasons, which I suspect may be partially financial and/or political in nature. 

This issue must therefore be addressed by political and financial means. My recommendation is for legislation that mandates lower reimbursement rates for health care systems and providers that refuse to offer full contraceptive options to women. If they do not provide full care, they do not get full payment for services. The money saved by reduced reimbursements could then fund federal women’s health clinics in areas dominated by “religious” health care systems that would guarantee full reproductive health options to all.

Name and practice location withheld

Remove Medicaid barriers to postpartum sterilization
An issue not addressed in Dr. Barbieri’s Editorial is that of women who, after appropriate and extensive counseling by a physician and with a full understanding of the reproductive implications and the possible adverse effect of additional pregnancies on their health and life, decide for permanent contraception. A woman’s opportunity to obtain postpartum or interval contraceptive procedure varies by her insurance coverage, which is indirectly associated with her ethnicity or race.

In 1979, Medicaid Title XIX imposed a 30-day interval between the signing of the sterilization informed consent by the patient and the performance of the procedure. These regulations are still in effect today. What was instituted to protect vulnerable populations from coerced methods in the 1970s represents an anachronistic and archaic approach in the 21st Century. This regulation discriminates against low-income and minority women whose health care is covered by public insurance yet who are frequently at highest risk for unintended and possible risky pregnancy or abortion. In simple words, this imposition violates the standards of justice, beneficence, and nonmaleficence as it treats publicly insured women differently from privately insured women.

The American Medical Association and the American College of Obstetricians and Gynecologists¹ state that this regulation must be revised and charged practitioners to develop policies and procedures to ensure all women who desire postpartum sterilization can receive it. It is incumbent upon all women’s health care physicians to see that this barrier is removed.

Federico G. Mariona, MD, MHSA
Dearborn, Michigan

Reference

Educate the sexual partners of at-risk women
It always strikes me how little emphasis is placed on including the sexual partners of women with serious medical problems in the dialogue about responsibility for at-risk pregnancy. As advocates for women’s health, we should educate the couple about vasectomy and liberally provide referrals. Community outreach to help men understand how they can protect their partner from potentially dangerous unwanted pregnancy is extremely important and not stressed enough. Vasectomy is a quick, safe procedure performed in a physician’s office under local anesthesia. Why should any woman who has already risked her life carrying and delivering a baby be required to bear the contraceptive burden when there is a safe and convenient alternative?

Emily Gubert, MD
East Islip, New York

Dr. Barbieri responds
I thank Drs. Will, Mariona, and Gubert and the anonymous author for their wonderful recommendations on approaches to help improve contraceptive care for women. I agree with Dr. Will that the EHR is a valuable tool to advance contraceptive care. The anonymous author and Dr. Mariona make the critically important point that all women should have access to desired contraception without any barriers based on institutional beliefs or government regulations. The patient’s needs should be prioritized in all medical decision making. I agree with Dr. Gubert that including the male partner in the care process is an important part of effective contraception for women. I enthusiastically agree with her that the best permanent contraceptive for a stable couple is vasectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“CAN WE SOLVE THE PROBLEM OF INADEQUATE CONTRACEPTION FOR WOMEN AT HIGH RISK FOR ADVERSE PREGNANCY OUTCOMES?”
ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2016)

“Contraception as a vital sign”
In his recent Editorial Dr. Barbieri asked for ideas to improve contraception counseling for women with medical problems that put them at risk for adverse pregnancy outcomes. His idea of “contraception status as a vital sign” is applied in our very large group practice in Northern California using the electronic health record (EHR).

Over 10 years ago, I attempted to put a hard stop in the EHR to require documentation that women of reproductive age be evaluated for contraception. This scheme seemed to be too cumbersome and was rejected at the time.

The idea was not abandoned, however. Medical assistants must now document a means of contraception for each woman of reproductive age. This does not guarantee that a physician will look at the information, but it is a step in the right direction.

My hope is that someday we will have automatic contraception as a vital sign documentation for all reproductive-age women, including “children” who are documented as menstruating. In the meantime, thank you for highlighting this critical issue.

Tia Will, MD
Sacramento, California

Reduce reimbursement when standard of care is not met
When I read Dr. Barbieri’s Editorial, I was surprised that he avoided the elephant in the room: the current political climate of denying contraception to women, including the defunding of Planned Parenthood and the Supreme Court decision to allow corporations to deny contraceptive coverage for religious issues.

Although I am not currently involved in women’s health, I do work under the auspices of a large Catholic health care system in the United States. Here, all employees are prohibited from providing contraceptive procedures, prescriptions, or even counseling unless it is a Natural Family Planning/ Fertility Awareness Method. These employees also are not provided individual contraceptive health coverage by their employer; this coverage is provided by the federal government thanks to the Affordable Care Act.

Contraception is part of the standard of care for women. However, many women are denied this standard of care due to “religious” reasons, which I suspect may be partially financial and/or political in nature. 

This issue must therefore be addressed by political and financial means. My recommendation is for legislation that mandates lower reimbursement rates for health care systems and providers that refuse to offer full contraceptive options to women. If they do not provide full care, they do not get full payment for services. The money saved by reduced reimbursements could then fund federal women’s health clinics in areas dominated by “religious” health care systems that would guarantee full reproductive health options to all.

Name and practice location withheld

Remove Medicaid barriers to postpartum sterilization
An issue not addressed in Dr. Barbieri’s Editorial is that of women who, after appropriate and extensive counseling by a physician and with a full understanding of the reproductive implications and the possible adverse effect of additional pregnancies on their health and life, decide for permanent contraception. A woman’s opportunity to obtain postpartum or interval contraceptive procedure varies by her insurance coverage, which is indirectly associated with her ethnicity or race.

In 1979, Medicaid Title XIX imposed a 30-day interval between the signing of the sterilization informed consent by the patient and the performance of the procedure. These regulations are still in effect today. What was instituted to protect vulnerable populations from coerced methods in the 1970s represents an anachronistic and archaic approach in the 21st Century. This regulation discriminates against low-income and minority women whose health care is covered by public insurance yet who are frequently at highest risk for unintended and possible risky pregnancy or abortion. In simple words, this imposition violates the standards of justice, beneficence, and nonmaleficence as it treats publicly insured women differently from privately insured women.

The American Medical Association and the American College of Obstetricians and Gynecologists¹ state that this regulation must be revised and charged practitioners to develop policies and procedures to ensure all women who desire postpartum sterilization can receive it. It is incumbent upon all women’s health care physicians to see that this barrier is removed.

Federico G. Mariona, MD, MHSA
Dearborn, Michigan

Reference

Educate the sexual partners of at-risk women
It always strikes me how little emphasis is placed on including the sexual partners of women with serious medical problems in the dialogue about responsibility for at-risk pregnancy. As advocates for women’s health, we should educate the couple about vasectomy and liberally provide referrals. Community outreach to help men understand how they can protect their partner from potentially dangerous unwanted pregnancy is extremely important and not stressed enough. Vasectomy is a quick, safe procedure performed in a physician’s office under local anesthesia. Why should any woman who has already risked her life carrying and delivering a baby be required to bear the contraceptive burden when there is a safe and convenient alternative?

Emily Gubert, MD
East Islip, New York

Dr. Barbieri responds
I thank Drs. Will, Mariona, and Gubert and the anonymous author for their wonderful recommendations on approaches to help improve contraceptive care for women. I agree with Dr. Will that the EHR is a valuable tool to advance contraceptive care. The anonymous author and Dr. Mariona make the critically important point that all women should have access to desired contraception without any barriers based on institutional beliefs or government regulations. The patient’s needs should be prioritized in all medical decision making. I agree with Dr. Gubert that including the male partner in the care process is an important part of effective contraception for women. I enthusiastically agree with her that the best permanent contraceptive for a stable couple is vasectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Yesterday, my secretary passed a message that someone from television had called with a question. Not knowing what to expect, but trying to be helpful, I returned the call that afternoon.

The fellow was nice enough, and explained he worked for a marketing company. A vitamin company had hired him to promote an over-the-counter supplement to treat Alzheimer’s disease, and he was looking for a neurologist to endorse it in an infomercial. He said I’d be compensated $5,000-$10,000 for the spot.

That’s a pretty decent chunk of change. I could use it. For a few seconds I hemmed and hawed, trying to think of a way to rationalize it. Then I realized ... I just couldn’t. I politely told him “No,” and got off the phone.

I know they’ll find someone to do it. But I just can’t. I’m sure they have some data to back it up, but crappy research papers are a dime a dozen.

I spend a lot of time explaining studies and data to those affected by this terrible disease. I’m trying to help them work their way through a maze of tests, treatments of limited benefit, and reasonable expectations.

Sadly, as with all tragic and incurable diseases, there’s no shortage of hucksters trying to take advantage of the desperate. Part of my job is to help people understand this. They bring in ads from magazines and newspaper promising miracle cures for a host of awful illnesses. I can’t stop them from buying it, but I want to do my best to warn them it’s a scam.

I can’t do that if I switch sides. Once I start plugging non–FDA-approved, non–clinically meaningful junk on late-night TV, I’ve joined the snake-oil salesmen of yesteryear.

I owe my patients better than that. They trust me to help them and to do what’s right.

Like everyone else, I don’t have a perfect reputation, but outside of my online reviews, I think I’m reasonably well thought of in the local community. A decent reputation takes years to build and one crappy decision to lose. I don’t want to do that either.

And under all that, I still have to believe in myself. That everyday I’m trying to do what’s right for people. Because if I’m not doing that, it’s time to hang up my reflex hammer. The first person I have to face every morning is in the mirror. I want to be able to look at him and still believe he’s doing the best he can for those who need his help.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Yesterday, my secretary passed a message that someone from television had called with a question. Not knowing what to expect, but trying to be helpful, I returned the call that afternoon.

The fellow was nice enough, and explained he worked for a marketing company. A vitamin company had hired him to promote an over-the-counter supplement to treat Alzheimer’s disease, and he was looking for a neurologist to endorse it in an infomercial. He said I’d be compensated $5,000-$10,000 for the spot.

That’s a pretty decent chunk of change. I could use it. For a few seconds I hemmed and hawed, trying to think of a way to rationalize it. Then I realized ... I just couldn’t. I politely told him “No,” and got off the phone.

I know they’ll find someone to do it. But I just can’t. I’m sure they have some data to back it up, but crappy research papers are a dime a dozen.

I spend a lot of time explaining studies and data to those affected by this terrible disease. I’m trying to help them work their way through a maze of tests, treatments of limited benefit, and reasonable expectations.

Sadly, as with all tragic and incurable diseases, there’s no shortage of hucksters trying to take advantage of the desperate. Part of my job is to help people understand this. They bring in ads from magazines and newspaper promising miracle cures for a host of awful illnesses. I can’t stop them from buying it, but I want to do my best to warn them it’s a scam.

I can’t do that if I switch sides. Once I start plugging non–FDA-approved, non–clinically meaningful junk on late-night TV, I’ve joined the snake-oil salesmen of yesteryear.

I owe my patients better than that. They trust me to help them and to do what’s right.

Like everyone else, I don’t have a perfect reputation, but outside of my online reviews, I think I’m reasonably well thought of in the local community. A decent reputation takes years to build and one crappy decision to lose. I don’t want to do that either.

And under all that, I still have to believe in myself. That everyday I’m trying to do what’s right for people. Because if I’m not doing that, it’s time to hang up my reflex hammer. The first person I have to face every morning is in the mirror. I want to be able to look at him and still believe he’s doing the best he can for those who need his help.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Yesterday, my secretary passed a message that someone from television had called with a question. Not knowing what to expect, but trying to be helpful, I returned the call that afternoon.

The fellow was nice enough, and explained he worked for a marketing company. A vitamin company had hired him to promote an over-the-counter supplement to treat Alzheimer’s disease, and he was looking for a neurologist to endorse it in an infomercial. He said I’d be compensated $5,000-$10,000 for the spot.

That’s a pretty decent chunk of change. I could use it. For a few seconds I hemmed and hawed, trying to think of a way to rationalize it. Then I realized ... I just couldn’t. I politely told him “No,” and got off the phone.

I know they’ll find someone to do it. But I just can’t. I’m sure they have some data to back it up, but crappy research papers are a dime a dozen.

I spend a lot of time explaining studies and data to those affected by this terrible disease. I’m trying to help them work their way through a maze of tests, treatments of limited benefit, and reasonable expectations.

Sadly, as with all tragic and incurable diseases, there’s no shortage of hucksters trying to take advantage of the desperate. Part of my job is to help people understand this. They bring in ads from magazines and newspaper promising miracle cures for a host of awful illnesses. I can’t stop them from buying it, but I want to do my best to warn them it’s a scam.

I can’t do that if I switch sides. Once I start plugging non–FDA-approved, non–clinically meaningful junk on late-night TV, I’ve joined the snake-oil salesmen of yesteryear.

I owe my patients better than that. They trust me to help them and to do what’s right.

Like everyone else, I don’t have a perfect reputation, but outside of my online reviews, I think I’m reasonably well thought of in the local community. A decent reputation takes years to build and one crappy decision to lose. I don’t want to do that either.

And under all that, I still have to believe in myself. That everyday I’m trying to do what’s right for people. Because if I’m not doing that, it’s time to hang up my reflex hammer. The first person I have to face every morning is in the mirror. I want to be able to look at him and still believe he’s doing the best he can for those who need his help.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Endometriosis is a common condition, occurring in this country in 1 of 10 women of reproductive age. An association between endometriosis and subsequent ovarian carcinoma has been reported for decades, yet it is only recently that our knowledge has deepened enough to support more rational methods for preventing the malignancy.

Each year, approximately 22,000 new cases of ovarian cancer are diagnosed. The lifetime risk of developing this malignancy is low, but it is the deadliest of the gynecologic malignancies, with diagnosis usually made in advanced stages when prognosis is poor.

Endometriosis shows some characteristics of malignancy, such as the development of local and distant foci, and attachment to and invasion of other tissues with subsequent damage to these tissues. Endometriosis also is characterized by recurrent, unregulated cell proliferation and estrogen-dependent growth.

Our attempts during the past 2 decades to detect ovarian carcinoma at the early stages through a combined screening modality involving transvaginal ultrasound and a test for the serum level of cancer antigen 125 have failed to provide any survival benefit or even any measurable reduction in morbidity. Today, early-stage ovarian carcinoma, which has a 5-year survival rate of more than 90%, is diagnosed in only a minority of women.

There is good news, however. In recent years our insight into the pathophysiology of ovarian cancer has deepened, providing us with a new paradigm for ovarian cancer pathogenesis that divides ovarian epithelial carcinoma into two distinct types with distinct molecular profiles – one which originates largely in the distal portion of the fallopian tube and the other which traces back to endometriosis.

This new paradigm strengthens and helps to explain the reported association between endometriosis and ovarian cancer. It also has important clinical implications for current practice. While we have much more to learn about the etiology of endometriosis and the causes of malignant transformation, our current knowledge provides a strong rationale for identification and close monitoring of some patients with endometriosis deemed at risk for ovarian cancer, risk-reducing medical management, earlier and more meticulous surgical treatment, and close monitoring.

By combining this new approach to endometriosis with consideration of salpingectomy after completion of childbearing, we have an unprecedented opportunity to reduce the incidence of epithelial ovarian cancer.

Dual pathogenesis

The majority of ovarian cancers are of epithelial origin and fall into four histologic categories: serous, endometrioid, clear cell, and mucinous. In recent years, we have gained a deeper understanding of the pathogenesis of ovarian carcinoma, with an array of epidemiologic, histologic, and molecular data showing us that epithelial ovarian cancers are also of two distinct types (Am J Obstet Gynecol. 2015 Sep;213[3]:262-7).

One of these types, a high-grade serous carcinoma, appears to arise in many cases in the epithelium of the fallopian tube. The other type of tumor is a low-grade carcinoma – particularly of the endometrioid and clear cell histologic subtypes – that originates largely from ovarian endometriotic lesions or from borderline serous tumors in the case of serous histology.

The majority of diagnosed stage 1 ovarian cancers are carcinomas of this low-grade type and not high-grade serous carcinomas. In a study of 76 consecutive stage 1 carcinomas, investigators found that ovarian endometriosis was present in 40 of the 76 cases. More than two-thirds of the 76 cases (71%) were nonserous cancers, and almost all of these cases were associated with endometriosis based on histologic examination (Fertil Steril. 2007 Oct;88[4]:906-10).

This study was among the first to show that the majority of stage 1 ovarian carcinomas are not high-grade serous carcinomas, but rather nonserous, primarily endometrioid and clear cell, cancers. The research demonstrated that endometriosis should be viewed as a potential precursor lesion to specific subtypes of ovarian cancer.

The malignant transformation of endometriosis was first suggested by Dr. J. A. Sampson in 1925, and a number of studies – in addition to the 2007 landmark study – have since described ovarian cancer arising from endometriosis, based on the frequent co-occurrence in surgical specimens.

Most recently, a study from the Ovarian Cancer Association Consortium (OCAC) found that women who reported a history of endometriosis had a significantly higher risk of developing ovarian cancer than the general population (odds ratio, 1.46).

Investigators of this critical study pooled data from 13 ovarian cancer case-control studies involving more than 13,226 controls and 7,911 women with invasive epithelial ovarian cancer – 818 (6.2%) and 738 (9.3%) of whom, respectively, reported a history of endometriosis. Specifically, they determined that self-reported endometriosis was associated with a 3.05-fold increased risk for clear cell invasive ovarian cancer and a 2.04-fold increased risk of endometrioid ovarian cancer.

Moreover, a significant association between preexisting endometriosis and low-grade serous invasive ovarian cancer (OR, 2.11) was demonstrated, while no association was found between endometriosis and the risk of high-grade serous invasive ovarian cancer (Lancet Oncol. 2012 Apr;13[4]:385-94).

A second recently published report – a meta-analysis of 20 case-control and 15 cohort studies published between 1990 and 2012 and involving more than 444,000 patients – found that endometriosis increased cancer risk in case-control or two-arm cohort studies by 27% (relative risk, 1.265) and by approximately 80% in single-arm cohort studies (standard incidence ratio, 1.797). Endometrioid and clear cell carcinomas were more common in endometriosis-associated ovarian cancer, while serous carcinoma was less frequent (Br J Cancer. 2014 Apr 2;110[7]:1878-90).

Findings of both of these large studies have served to clarify the association between endometriosis and specific histologic subtypes and suggested that there are important differences in the pathogenesis of low-grade and high-grade serous ovarian carcinomas.

Clinical implications

It is not clear what causes malignant transformation or what predisposes some patients with endometriosis to develop ovarian cancer, but the risk likely involves genetic and epigenetic influences as well as immunologic, inflammatory, and hormonal factors.

The molecular profiles of the main two types of ovarian cancer are different: While the majority of high-grade serous ovarian tumors are characterized by TP53 mutations, the low-grade carcinomas are characterized by a variety of mutations, including KRAS, BRAF, ERBB2, CTNNB1, and BCL2 mutations.

There currently are not enough data to recommend genetic screening tests in patients with endometriosis, but our hope is that we eventually will be able to screen for “high-risk” endometriotic lesions by testing for genes specific to various histologic subtypes of low-grade ovarian cancer, or by finding and utilizing other biomarkers.

Courtesy of Dr. Farr Nezhat

In the meantime, we believe it is important to more thoroughly treat endometriosis and to identify and follow women with a history of the condition, especially those with a long-standing history, those with a history of endometriosis associated with infertility, and those with ovarian endometrioma. Each of these factors predisposes patients to a higher risk of malignant transformation.

Complete surgical resection of all visible endometriosis is the most effective treatment and will afford the best cancer prevention, even in women who are asymptomatic. In a recent Swedish national registry case-control study, women who underwent radical surgical excision of all visible endometriosis were significantly less likely (OR, 0.30) to develop ovarian cancer (Acta Obstet Gynecol Scand. 2013 May;92[5]:546-54).

Suppressive hormonal therapy is another treatment option for patients with no interest in conceiving. Most large endometriomas are functional ovarian cysts that have been invaded by cortical ovarian endometriosis or by small primary endometriomas (J Reprod Med. 1992 Sep;37[9]:771-6).

While hormonal therapy will not always result in complete regression of endometriotic lesions, it will decrease the recurrence rate of endometriomas and can be considered for long-term prevention of potentially premalignant lesions. It is most effective when it follows surgical excision of endometriomas and associated endometriosis.

A patient who has completed childbearing at the time of surgical resection may be offered bilateral salpingectomy, regardless of menopausal status. Salpingectomy in both average and high-risk populations (e.g., BRCA 1/2 carriers) not only prevents high-grade serous carcinoma by eliminating the site of origin, but also may decrease the risk of endometrioid and clear cell carcinoma by blocking the passageway that enables the flow of endometrium and factors that induce inflammation. It is estimated that the procedure reduces the risk of ovarian cancer by 40%.

Interestingly, tubal ligation has historically been shown to decrease the risk of ovarian cancer, and recent data have shown that the risk of endometrioid and clear cell carcinoma is cut even more than the risk of high-grade serous carcinoma (Int J Epidemiol. 2013 Apr;42[2]:579-89).

Courtesy Dr. Farr Nezhat

The Society of Gynecologic Oncology recommends that risk-reducing salpingectomy be considered at the time of hysterectomy or other abdominal or pelvic surgery, and in lieu of tubal ligation. The American College of Obstetricians and Gynecologists similarly has stated that prophylactic salpingectomy may offer clinicians the opportunity to prevent ovarian cancer in their patients. Salpingectomy is an important option for all patients, but is especially important when the fallopian tubes are found to be damaged by endometriosis and/or pelvic inflammatory disease. When imaging studies show that endometriomas are present and resection is not performed, pelvic ultrasound should become part of the patient’s routine examination.

Most endometriomas have a homogeneous appearance; any significant increase in size or a change in the homogeneous cystic characteristics to a more heterogeneous appearance with mural components should raise suspicion about malignant change.

It can be difficult to detect relatively small endocystic components with ultrasound, so if there is any doubt about whether there is some heterogeneous consistency, an MRI should be performed. MRI is showing more promise in detecting malignant change. Hyperdense mural nodules within the ovary and rapid growth of an endometrioma have both been associated with malignant transformation and can be seen on these images.

In a cohort study comparing MRI findings of 10 patients with ovarian adenocarcinoma to 10 patients with benign endometriomas, investigators found mural nodules in all 10 malignancies but in only three of the benign cases (AJR Am J Roentgenol. 2000 Nov;175[5]:1423-30).

Long-term follow-up is necessary to understand the timeline of transformation in patients with mural nodules. This together with increasing knowledge of molecular events underpinning evolution of endometriosis will lead to better screening and preventive strategies.

Dr. Nezhat is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook. He reported having no financial disclosures.

Endometriosis is a common condition, occurring in this country in 1 of 10 women of reproductive age. An association between endometriosis and subsequent ovarian carcinoma has been reported for decades, yet it is only recently that our knowledge has deepened enough to support more rational methods for preventing the malignancy.

Each year, approximately 22,000 new cases of ovarian cancer are diagnosed. The lifetime risk of developing this malignancy is low, but it is the deadliest of the gynecologic malignancies, with diagnosis usually made in advanced stages when prognosis is poor.

Endometriosis shows some characteristics of malignancy, such as the development of local and distant foci, and attachment to and invasion of other tissues with subsequent damage to these tissues. Endometriosis also is characterized by recurrent, unregulated cell proliferation and estrogen-dependent growth.

Our attempts during the past 2 decades to detect ovarian carcinoma at the early stages through a combined screening modality involving transvaginal ultrasound and a test for the serum level of cancer antigen 125 have failed to provide any survival benefit or even any measurable reduction in morbidity. Today, early-stage ovarian carcinoma, which has a 5-year survival rate of more than 90%, is diagnosed in only a minority of women.

There is good news, however. In recent years our insight into the pathophysiology of ovarian cancer has deepened, providing us with a new paradigm for ovarian cancer pathogenesis that divides ovarian epithelial carcinoma into two distinct types with distinct molecular profiles – one which originates largely in the distal portion of the fallopian tube and the other which traces back to endometriosis.

This new paradigm strengthens and helps to explain the reported association between endometriosis and ovarian cancer. It also has important clinical implications for current practice. While we have much more to learn about the etiology of endometriosis and the causes of malignant transformation, our current knowledge provides a strong rationale for identification and close monitoring of some patients with endometriosis deemed at risk for ovarian cancer, risk-reducing medical management, earlier and more meticulous surgical treatment, and close monitoring.

By combining this new approach to endometriosis with consideration of salpingectomy after completion of childbearing, we have an unprecedented opportunity to reduce the incidence of epithelial ovarian cancer.

Dual pathogenesis

The majority of ovarian cancers are of epithelial origin and fall into four histologic categories: serous, endometrioid, clear cell, and mucinous. In recent years, we have gained a deeper understanding of the pathogenesis of ovarian carcinoma, with an array of epidemiologic, histologic, and molecular data showing us that epithelial ovarian cancers are also of two distinct types (Am J Obstet Gynecol. 2015 Sep;213[3]:262-7).

One of these types, a high-grade serous carcinoma, appears to arise in many cases in the epithelium of the fallopian tube. The other type of tumor is a low-grade carcinoma – particularly of the endometrioid and clear cell histologic subtypes – that originates largely from ovarian endometriotic lesions or from borderline serous tumors in the case of serous histology.

The majority of diagnosed stage 1 ovarian cancers are carcinomas of this low-grade type and not high-grade serous carcinomas. In a study of 76 consecutive stage 1 carcinomas, investigators found that ovarian endometriosis was present in 40 of the 76 cases. More than two-thirds of the 76 cases (71%) were nonserous cancers, and almost all of these cases were associated with endometriosis based on histologic examination (Fertil Steril. 2007 Oct;88[4]:906-10).

This study was among the first to show that the majority of stage 1 ovarian carcinomas are not high-grade serous carcinomas, but rather nonserous, primarily endometrioid and clear cell, cancers. The research demonstrated that endometriosis should be viewed as a potential precursor lesion to specific subtypes of ovarian cancer.

The malignant transformation of endometriosis was first suggested by Dr. J. A. Sampson in 1925, and a number of studies – in addition to the 2007 landmark study – have since described ovarian cancer arising from endometriosis, based on the frequent co-occurrence in surgical specimens.

Most recently, a study from the Ovarian Cancer Association Consortium (OCAC) found that women who reported a history of endometriosis had a significantly higher risk of developing ovarian cancer than the general population (odds ratio, 1.46).

Investigators of this critical study pooled data from 13 ovarian cancer case-control studies involving more than 13,226 controls and 7,911 women with invasive epithelial ovarian cancer – 818 (6.2%) and 738 (9.3%) of whom, respectively, reported a history of endometriosis. Specifically, they determined that self-reported endometriosis was associated with a 3.05-fold increased risk for clear cell invasive ovarian cancer and a 2.04-fold increased risk of endometrioid ovarian cancer.

Moreover, a significant association between preexisting endometriosis and low-grade serous invasive ovarian cancer (OR, 2.11) was demonstrated, while no association was found between endometriosis and the risk of high-grade serous invasive ovarian cancer (Lancet Oncol. 2012 Apr;13[4]:385-94).

A second recently published report – a meta-analysis of 20 case-control and 15 cohort studies published between 1990 and 2012 and involving more than 444,000 patients – found that endometriosis increased cancer risk in case-control or two-arm cohort studies by 27% (relative risk, 1.265) and by approximately 80% in single-arm cohort studies (standard incidence ratio, 1.797). Endometrioid and clear cell carcinomas were more common in endometriosis-associated ovarian cancer, while serous carcinoma was less frequent (Br J Cancer. 2014 Apr 2;110[7]:1878-90).

Findings of both of these large studies have served to clarify the association between endometriosis and specific histologic subtypes and suggested that there are important differences in the pathogenesis of low-grade and high-grade serous ovarian carcinomas.

Clinical implications

It is not clear what causes malignant transformation or what predisposes some patients with endometriosis to develop ovarian cancer, but the risk likely involves genetic and epigenetic influences as well as immunologic, inflammatory, and hormonal factors.

The molecular profiles of the main two types of ovarian cancer are different: While the majority of high-grade serous ovarian tumors are characterized by TP53 mutations, the low-grade carcinomas are characterized by a variety of mutations, including KRAS, BRAF, ERBB2, CTNNB1, and BCL2 mutations.

There currently are not enough data to recommend genetic screening tests in patients with endometriosis, but our hope is that we eventually will be able to screen for “high-risk” endometriotic lesions by testing for genes specific to various histologic subtypes of low-grade ovarian cancer, or by finding and utilizing other biomarkers.

Courtesy of Dr. Farr Nezhat

In the meantime, we believe it is important to more thoroughly treat endometriosis and to identify and follow women with a history of the condition, especially those with a long-standing history, those with a history of endometriosis associated with infertility, and those with ovarian endometrioma. Each of these factors predisposes patients to a higher risk of malignant transformation.

Complete surgical resection of all visible endometriosis is the most effective treatment and will afford the best cancer prevention, even in women who are asymptomatic. In a recent Swedish national registry case-control study, women who underwent radical surgical excision of all visible endometriosis were significantly less likely (OR, 0.30) to develop ovarian cancer (Acta Obstet Gynecol Scand. 2013 May;92[5]:546-54).

Suppressive hormonal therapy is another treatment option for patients with no interest in conceiving. Most large endometriomas are functional ovarian cysts that have been invaded by cortical ovarian endometriosis or by small primary endometriomas (J Reprod Med. 1992 Sep;37[9]:771-6).

While hormonal therapy will not always result in complete regression of endometriotic lesions, it will decrease the recurrence rate of endometriomas and can be considered for long-term prevention of potentially premalignant lesions. It is most effective when it follows surgical excision of endometriomas and associated endometriosis.

A patient who has completed childbearing at the time of surgical resection may be offered bilateral salpingectomy, regardless of menopausal status. Salpingectomy in both average and high-risk populations (e.g., BRCA 1/2 carriers) not only prevents high-grade serous carcinoma by eliminating the site of origin, but also may decrease the risk of endometrioid and clear cell carcinoma by blocking the passageway that enables the flow of endometrium and factors that induce inflammation. It is estimated that the procedure reduces the risk of ovarian cancer by 40%.

Interestingly, tubal ligation has historically been shown to decrease the risk of ovarian cancer, and recent data have shown that the risk of endometrioid and clear cell carcinoma is cut even more than the risk of high-grade serous carcinoma (Int J Epidemiol. 2013 Apr;42[2]:579-89).

Courtesy Dr. Farr Nezhat

The Society of Gynecologic Oncology recommends that risk-reducing salpingectomy be considered at the time of hysterectomy or other abdominal or pelvic surgery, and in lieu of tubal ligation. The American College of Obstetricians and Gynecologists similarly has stated that prophylactic salpingectomy may offer clinicians the opportunity to prevent ovarian cancer in their patients. Salpingectomy is an important option for all patients, but is especially important when the fallopian tubes are found to be damaged by endometriosis and/or pelvic inflammatory disease. When imaging studies show that endometriomas are present and resection is not performed, pelvic ultrasound should become part of the patient’s routine examination.

Most endometriomas have a homogeneous appearance; any significant increase in size or a change in the homogeneous cystic characteristics to a more heterogeneous appearance with mural components should raise suspicion about malignant change.

It can be difficult to detect relatively small endocystic components with ultrasound, so if there is any doubt about whether there is some heterogeneous consistency, an MRI should be performed. MRI is showing more promise in detecting malignant change. Hyperdense mural nodules within the ovary and rapid growth of an endometrioma have both been associated with malignant transformation and can be seen on these images.

In a cohort study comparing MRI findings of 10 patients with ovarian adenocarcinoma to 10 patients with benign endometriomas, investigators found mural nodules in all 10 malignancies but in only three of the benign cases (AJR Am J Roentgenol. 2000 Nov;175[5]:1423-30).

Long-term follow-up is necessary to understand the timeline of transformation in patients with mural nodules. This together with increasing knowledge of molecular events underpinning evolution of endometriosis will lead to better screening and preventive strategies.

Dr. Nezhat is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook. He reported having no financial disclosures.

Endometriosis is a common condition, occurring in this country in 1 of 10 women of reproductive age. An association between endometriosis and subsequent ovarian carcinoma has been reported for decades, yet it is only recently that our knowledge has deepened enough to support more rational methods for preventing the malignancy.

Each year, approximately 22,000 new cases of ovarian cancer are diagnosed. The lifetime risk of developing this malignancy is low, but it is the deadliest of the gynecologic malignancies, with diagnosis usually made in advanced stages when prognosis is poor.

Endometriosis shows some characteristics of malignancy, such as the development of local and distant foci, and attachment to and invasion of other tissues with subsequent damage to these tissues. Endometriosis also is characterized by recurrent, unregulated cell proliferation and estrogen-dependent growth.

Our attempts during the past 2 decades to detect ovarian carcinoma at the early stages through a combined screening modality involving transvaginal ultrasound and a test for the serum level of cancer antigen 125 have failed to provide any survival benefit or even any measurable reduction in morbidity. Today, early-stage ovarian carcinoma, which has a 5-year survival rate of more than 90%, is diagnosed in only a minority of women.

There is good news, however. In recent years our insight into the pathophysiology of ovarian cancer has deepened, providing us with a new paradigm for ovarian cancer pathogenesis that divides ovarian epithelial carcinoma into two distinct types with distinct molecular profiles – one which originates largely in the distal portion of the fallopian tube and the other which traces back to endometriosis.

This new paradigm strengthens and helps to explain the reported association between endometriosis and ovarian cancer. It also has important clinical implications for current practice. While we have much more to learn about the etiology of endometriosis and the causes of malignant transformation, our current knowledge provides a strong rationale for identification and close monitoring of some patients with endometriosis deemed at risk for ovarian cancer, risk-reducing medical management, earlier and more meticulous surgical treatment, and close monitoring.

By combining this new approach to endometriosis with consideration of salpingectomy after completion of childbearing, we have an unprecedented opportunity to reduce the incidence of epithelial ovarian cancer.

Dual pathogenesis

The majority of ovarian cancers are of epithelial origin and fall into four histologic categories: serous, endometrioid, clear cell, and mucinous. In recent years, we have gained a deeper understanding of the pathogenesis of ovarian carcinoma, with an array of epidemiologic, histologic, and molecular data showing us that epithelial ovarian cancers are also of two distinct types (Am J Obstet Gynecol. 2015 Sep;213[3]:262-7).

One of these types, a high-grade serous carcinoma, appears to arise in many cases in the epithelium of the fallopian tube. The other type of tumor is a low-grade carcinoma – particularly of the endometrioid and clear cell histologic subtypes – that originates largely from ovarian endometriotic lesions or from borderline serous tumors in the case of serous histology.

The majority of diagnosed stage 1 ovarian cancers are carcinomas of this low-grade type and not high-grade serous carcinomas. In a study of 76 consecutive stage 1 carcinomas, investigators found that ovarian endometriosis was present in 40 of the 76 cases. More than two-thirds of the 76 cases (71%) were nonserous cancers, and almost all of these cases were associated with endometriosis based on histologic examination (Fertil Steril. 2007 Oct;88[4]:906-10).

This study was among the first to show that the majority of stage 1 ovarian carcinomas are not high-grade serous carcinomas, but rather nonserous, primarily endometrioid and clear cell, cancers. The research demonstrated that endometriosis should be viewed as a potential precursor lesion to specific subtypes of ovarian cancer.

The malignant transformation of endometriosis was first suggested by Dr. J. A. Sampson in 1925, and a number of studies – in addition to the 2007 landmark study – have since described ovarian cancer arising from endometriosis, based on the frequent co-occurrence in surgical specimens.

Most recently, a study from the Ovarian Cancer Association Consortium (OCAC) found that women who reported a history of endometriosis had a significantly higher risk of developing ovarian cancer than the general population (odds ratio, 1.46).

Investigators of this critical study pooled data from 13 ovarian cancer case-control studies involving more than 13,226 controls and 7,911 women with invasive epithelial ovarian cancer – 818 (6.2%) and 738 (9.3%) of whom, respectively, reported a history of endometriosis. Specifically, they determined that self-reported endometriosis was associated with a 3.05-fold increased risk for clear cell invasive ovarian cancer and a 2.04-fold increased risk of endometrioid ovarian cancer.

Moreover, a significant association between preexisting endometriosis and low-grade serous invasive ovarian cancer (OR, 2.11) was demonstrated, while no association was found between endometriosis and the risk of high-grade serous invasive ovarian cancer (Lancet Oncol. 2012 Apr;13[4]:385-94).

A second recently published report – a meta-analysis of 20 case-control and 15 cohort studies published between 1990 and 2012 and involving more than 444,000 patients – found that endometriosis increased cancer risk in case-control or two-arm cohort studies by 27% (relative risk, 1.265) and by approximately 80% in single-arm cohort studies (standard incidence ratio, 1.797). Endometrioid and clear cell carcinomas were more common in endometriosis-associated ovarian cancer, while serous carcinoma was less frequent (Br J Cancer. 2014 Apr 2;110[7]:1878-90).

Findings of both of these large studies have served to clarify the association between endometriosis and specific histologic subtypes and suggested that there are important differences in the pathogenesis of low-grade and high-grade serous ovarian carcinomas.

Clinical implications

It is not clear what causes malignant transformation or what predisposes some patients with endometriosis to develop ovarian cancer, but the risk likely involves genetic and epigenetic influences as well as immunologic, inflammatory, and hormonal factors.

The molecular profiles of the main two types of ovarian cancer are different: While the majority of high-grade serous ovarian tumors are characterized by TP53 mutations, the low-grade carcinomas are characterized by a variety of mutations, including KRAS, BRAF, ERBB2, CTNNB1, and BCL2 mutations.

There currently are not enough data to recommend genetic screening tests in patients with endometriosis, but our hope is that we eventually will be able to screen for “high-risk” endometriotic lesions by testing for genes specific to various histologic subtypes of low-grade ovarian cancer, or by finding and utilizing other biomarkers.

Courtesy of Dr. Farr Nezhat

In the meantime, we believe it is important to more thoroughly treat endometriosis and to identify and follow women with a history of the condition, especially those with a long-standing history, those with a history of endometriosis associated with infertility, and those with ovarian endometrioma. Each of these factors predisposes patients to a higher risk of malignant transformation.

Complete surgical resection of all visible endometriosis is the most effective treatment and will afford the best cancer prevention, even in women who are asymptomatic. In a recent Swedish national registry case-control study, women who underwent radical surgical excision of all visible endometriosis were significantly less likely (OR, 0.30) to develop ovarian cancer (Acta Obstet Gynecol Scand. 2013 May;92[5]:546-54).

Suppressive hormonal therapy is another treatment option for patients with no interest in conceiving. Most large endometriomas are functional ovarian cysts that have been invaded by cortical ovarian endometriosis or by small primary endometriomas (J Reprod Med. 1992 Sep;37[9]:771-6).

While hormonal therapy will not always result in complete regression of endometriotic lesions, it will decrease the recurrence rate of endometriomas and can be considered for long-term prevention of potentially premalignant lesions. It is most effective when it follows surgical excision of endometriomas and associated endometriosis.

A patient who has completed childbearing at the time of surgical resection may be offered bilateral salpingectomy, regardless of menopausal status. Salpingectomy in both average and high-risk populations (e.g., BRCA 1/2 carriers) not only prevents high-grade serous carcinoma by eliminating the site of origin, but also may decrease the risk of endometrioid and clear cell carcinoma by blocking the passageway that enables the flow of endometrium and factors that induce inflammation. It is estimated that the procedure reduces the risk of ovarian cancer by 40%.

Interestingly, tubal ligation has historically been shown to decrease the risk of ovarian cancer, and recent data have shown that the risk of endometrioid and clear cell carcinoma is cut even more than the risk of high-grade serous carcinoma (Int J Epidemiol. 2013 Apr;42[2]:579-89).

Courtesy Dr. Farr Nezhat

The Society of Gynecologic Oncology recommends that risk-reducing salpingectomy be considered at the time of hysterectomy or other abdominal or pelvic surgery, and in lieu of tubal ligation. The American College of Obstetricians and Gynecologists similarly has stated that prophylactic salpingectomy may offer clinicians the opportunity to prevent ovarian cancer in their patients. Salpingectomy is an important option for all patients, but is especially important when the fallopian tubes are found to be damaged by endometriosis and/or pelvic inflammatory disease. When imaging studies show that endometriomas are present and resection is not performed, pelvic ultrasound should become part of the patient’s routine examination.

Most endometriomas have a homogeneous appearance; any significant increase in size or a change in the homogeneous cystic characteristics to a more heterogeneous appearance with mural components should raise suspicion about malignant change.

It can be difficult to detect relatively small endocystic components with ultrasound, so if there is any doubt about whether there is some heterogeneous consistency, an MRI should be performed. MRI is showing more promise in detecting malignant change. Hyperdense mural nodules within the ovary and rapid growth of an endometrioma have both been associated with malignant transformation and can be seen on these images.

In a cohort study comparing MRI findings of 10 patients with ovarian adenocarcinoma to 10 patients with benign endometriomas, investigators found mural nodules in all 10 malignancies but in only three of the benign cases (AJR Am J Roentgenol. 2000 Nov;175[5]:1423-30).

Long-term follow-up is necessary to understand the timeline of transformation in patients with mural nodules. This together with increasing knowledge of molecular events underpinning evolution of endometriosis will lead to better screening and preventive strategies.

Dr. Nezhat is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook. He reported having no financial disclosures.

During an ob.gyn. rotation, a medical student quickly learns the risks related to endometriosis; that is, pelvic pain, abnormal uterine bleeding, and infertility. With more experience, the young practitioner realizes the concern of unopposed estrogen therapy in patients with a history of endometriosis (i.e., cancer).

Now, in this excellent discussion by Dr. Farr Nezhat, for the current edition of the Master Class in Gynecologic Surgery, he describes the risk of endometriosis and ovarian cancer. Not only does Dr. Nezhat present data revealing the increased association between ovarian cancer and endometriosis, but he goes on to describe the usual type of epithelial ovarian cancer that is noted in the patient with endometriosis.

Dr. Nezhat describes women who appear to be predisposed to malignant transformation and provides current recommendations to lower the risk of malignancy in patients with endometriosis. This includes complete surgical resection of endometriosis, routine ultrasound/MRI if endometriosis is not resected, suppressive hormonal therapy, and bilateral salpingectomy. Moreover, Dr. Nezhat looks to the future and the possibility of genetic screening tests.

Dr. Nezhat is board certified in gynecologic oncology and is world renowned for his work with advanced laparoscopic and robotic surgery for the treatment of gynecologic cancers and complex benign conditions. He is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at State University of New York at Stony Brook.

His main areas of interest and research include early detection and treatment of early and advanced ovarian cancer, as well as cancer arising in endometriosis. Dr. Nezhat has authored and coauthored more than 200 medical and scientific manuscripts and book chapters.

Dr. Miller is a clinical associate professor at the University of Illinois at Chicago, and a past president of the AAGL and the International Society for Gynecologic Endoscopy (ISGE). He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/Society of Reproductive Surgery fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. Dr. Miller reported having no financial disclosures relevant to this column.

During an ob.gyn. rotation, a medical student quickly learns the risks related to endometriosis; that is, pelvic pain, abnormal uterine bleeding, and infertility. With more experience, the young practitioner realizes the concern of unopposed estrogen therapy in patients with a history of endometriosis (i.e., cancer).

Now, in this excellent discussion by Dr. Farr Nezhat, for the current edition of the Master Class in Gynecologic Surgery, he describes the risk of endometriosis and ovarian cancer. Not only does Dr. Nezhat present data revealing the increased association between ovarian cancer and endometriosis, but he goes on to describe the usual type of epithelial ovarian cancer that is noted in the patient with endometriosis.

Dr. Nezhat describes women who appear to be predisposed to malignant transformation and provides current recommendations to lower the risk of malignancy in patients with endometriosis. This includes complete surgical resection of endometriosis, routine ultrasound/MRI if endometriosis is not resected, suppressive hormonal therapy, and bilateral salpingectomy. Moreover, Dr. Nezhat looks to the future and the possibility of genetic screening tests.

Dr. Nezhat is board certified in gynecologic oncology and is world renowned for his work with advanced laparoscopic and robotic surgery for the treatment of gynecologic cancers and complex benign conditions. He is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at State University of New York at Stony Brook.

His main areas of interest and research include early detection and treatment of early and advanced ovarian cancer, as well as cancer arising in endometriosis. Dr. Nezhat has authored and coauthored more than 200 medical and scientific manuscripts and book chapters.

Dr. Miller is a clinical associate professor at the University of Illinois at Chicago, and a past president of the AAGL and the International Society for Gynecologic Endoscopy (ISGE). He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/Society of Reproductive Surgery fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. Dr. Miller reported having no financial disclosures relevant to this column.

During an ob.gyn. rotation, a medical student quickly learns the risks related to endometriosis; that is, pelvic pain, abnormal uterine bleeding, and infertility. With more experience, the young practitioner realizes the concern of unopposed estrogen therapy in patients with a history of endometriosis (i.e., cancer).

Now, in this excellent discussion by Dr. Farr Nezhat, for the current edition of the Master Class in Gynecologic Surgery, he describes the risk of endometriosis and ovarian cancer. Not only does Dr. Nezhat present data revealing the increased association between ovarian cancer and endometriosis, but he goes on to describe the usual type of epithelial ovarian cancer that is noted in the patient with endometriosis.

Dr. Nezhat describes women who appear to be predisposed to malignant transformation and provides current recommendations to lower the risk of malignancy in patients with endometriosis. This includes complete surgical resection of endometriosis, routine ultrasound/MRI if endometriosis is not resected, suppressive hormonal therapy, and bilateral salpingectomy. Moreover, Dr. Nezhat looks to the future and the possibility of genetic screening tests.

Dr. Nezhat is board certified in gynecologic oncology and is world renowned for his work with advanced laparoscopic and robotic surgery for the treatment of gynecologic cancers and complex benign conditions. He is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at State University of New York at Stony Brook.

His main areas of interest and research include early detection and treatment of early and advanced ovarian cancer, as well as cancer arising in endometriosis. Dr. Nezhat has authored and coauthored more than 200 medical and scientific manuscripts and book chapters.

Dr. Miller is a clinical associate professor at the University of Illinois at Chicago, and a past president of the AAGL and the International Society for Gynecologic Endoscopy (ISGE). He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/Society of Reproductive Surgery fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. Dr. Miller reported having no financial disclosures relevant to this column.

Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.

Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.

In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.

Terminology

The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.

In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.

©monkeybusinessimages/Thinkstock

Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.

Diagnosis

There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.

If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.

Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.

HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.

Management

Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.

If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.

There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.

In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).

The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.

Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].

Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.

Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.

In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.

Terminology

The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.

In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.

©monkeybusinessimages/Thinkstock

Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.

Diagnosis

There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.

If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.

Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.

HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.

Management

Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.

If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.

There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.

In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).

The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.

Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].

Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.

Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.

In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.

Terminology

The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.

In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.

©monkeybusinessimages/Thinkstock

Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.

Diagnosis

There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.

If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.

Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.

HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.

Management

Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.

If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.

There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.

In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).

The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.

Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].