Breast Cancer

Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than a GnRH agonist in achieving ovarian function suppression in women with breast cancer, results of a randomized trial show.

Ovarian function suppression was achieved more rapidly and maintained more effectively with degarelix, compared with triptorelin, in the premenopausal women who were receiving letrozole for neoadjuvant endocrine therapy, investigators said.

Adverse events including hot flashes and injection site reactions were reported more often with degarelix versus the GnRH agonist in this randomized, phase 2 trial of 51 subjects.

Additional research is needed to determine whether degarelix results in superior disease control versus the current standard of care, reported Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS in Milan, Italy, and coinvestigators.

“The study is hypothesis-generating, and supports later studies to assess whether maintenance of ovarian function suppression with degarelix translates into a better clinical outcome and is worth a trade-off of increased rate of some adverse events,” the researchers wrote. The report is in the Journal of Clinical Oncology.

Patients were randomly assigned to receive degarelix plus letrozole or triptorelin plus letrozole for six 28-day cycles. Degarelix was administered subcutaneously on day 1 of each cycle, while triptorelin was administered intramuscularly on day 1 of each cycle, and oral letrozole was to be taken daily. Surgery was performed a few weeks after the last injection.

All patients achieved optimal ovarian function suppression by the end of the first cycle. However, that endpoint was achieved significantly faster among patients in the degarelix arm, at a median of 3 days, versus a median of 14 days for the GnRH agonist, the investigators reported.

The optimal ovarian function suppression was seen three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than 001), they added.

One hundred percent of patients receiving degarelix and letrozole maintained optimal ovarian function suppression throughout the study, while about 15% of patients assigned to triptorelin had suboptimal suppression after that first cycle.

The group of patients receiving degarelix had a higher rate of node-negative disease at surgery, and a higher rate of breast-conserving surgery compared with the triptorelin group, the investigators said.

There were two grade 3 adverse events, hypertension and anemia, which both occurred in the triptorelin group, and no grade 4 adverse events. The most common adverse events reported were hot flashes, occurring in 80.0% and 69.2% of the degarelix and triptorelin groups, respectively; arthralgias in 32.0% and 53.8%; insomnia in 24.0% and 11.5%; injection site reactions in 24.0% and 0%; and nausea in 16.0% and 3.8%.

The study was supported by Ferring, and by the International Breast Cancer Study Group via Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland, Oncosuisse, Swiss Cancer League, and the Foundation for Clinical Cancer Research of Eastern Switzerland. The authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.

SOURCE: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. doi: 10.1200/JCO.18.00296.

Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than a GnRH agonist in achieving ovarian function suppression in women with breast cancer, results of a randomized trial show.

Ovarian function suppression was achieved more rapidly and maintained more effectively with degarelix, compared with triptorelin, in the premenopausal women who were receiving letrozole for neoadjuvant endocrine therapy, investigators said.

Adverse events including hot flashes and injection site reactions were reported more often with degarelix versus the GnRH agonist in this randomized, phase 2 trial of 51 subjects.

Additional research is needed to determine whether degarelix results in superior disease control versus the current standard of care, reported Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS in Milan, Italy, and coinvestigators.

“The study is hypothesis-generating, and supports later studies to assess whether maintenance of ovarian function suppression with degarelix translates into a better clinical outcome and is worth a trade-off of increased rate of some adverse events,” the researchers wrote. The report is in the Journal of Clinical Oncology.

Patients were randomly assigned to receive degarelix plus letrozole or triptorelin plus letrozole for six 28-day cycles. Degarelix was administered subcutaneously on day 1 of each cycle, while triptorelin was administered intramuscularly on day 1 of each cycle, and oral letrozole was to be taken daily. Surgery was performed a few weeks after the last injection.

All patients achieved optimal ovarian function suppression by the end of the first cycle. However, that endpoint was achieved significantly faster among patients in the degarelix arm, at a median of 3 days, versus a median of 14 days for the GnRH agonist, the investigators reported.

The optimal ovarian function suppression was seen three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than 001), they added.

One hundred percent of patients receiving degarelix and letrozole maintained optimal ovarian function suppression throughout the study, while about 15% of patients assigned to triptorelin had suboptimal suppression after that first cycle.

The group of patients receiving degarelix had a higher rate of node-negative disease at surgery, and a higher rate of breast-conserving surgery compared with the triptorelin group, the investigators said.

There were two grade 3 adverse events, hypertension and anemia, which both occurred in the triptorelin group, and no grade 4 adverse events. The most common adverse events reported were hot flashes, occurring in 80.0% and 69.2% of the degarelix and triptorelin groups, respectively; arthralgias in 32.0% and 53.8%; insomnia in 24.0% and 11.5%; injection site reactions in 24.0% and 0%; and nausea in 16.0% and 3.8%.

The study was supported by Ferring, and by the International Breast Cancer Study Group via Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland, Oncosuisse, Swiss Cancer League, and the Foundation for Clinical Cancer Research of Eastern Switzerland. The authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.

SOURCE: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. doi: 10.1200/JCO.18.00296.

Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than a GnRH agonist in achieving ovarian function suppression in women with breast cancer, results of a randomized trial show.

Ovarian function suppression was achieved more rapidly and maintained more effectively with degarelix, compared with triptorelin, in the premenopausal women who were receiving letrozole for neoadjuvant endocrine therapy, investigators said.

Adverse events including hot flashes and injection site reactions were reported more often with degarelix versus the GnRH agonist in this randomized, phase 2 trial of 51 subjects.

Additional research is needed to determine whether degarelix results in superior disease control versus the current standard of care, reported Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS in Milan, Italy, and coinvestigators.

“The study is hypothesis-generating, and supports later studies to assess whether maintenance of ovarian function suppression with degarelix translates into a better clinical outcome and is worth a trade-off of increased rate of some adverse events,” the researchers wrote. The report is in the Journal of Clinical Oncology.

Patients were randomly assigned to receive degarelix plus letrozole or triptorelin plus letrozole for six 28-day cycles. Degarelix was administered subcutaneously on day 1 of each cycle, while triptorelin was administered intramuscularly on day 1 of each cycle, and oral letrozole was to be taken daily. Surgery was performed a few weeks after the last injection.

All patients achieved optimal ovarian function suppression by the end of the first cycle. However, that endpoint was achieved significantly faster among patients in the degarelix arm, at a median of 3 days, versus a median of 14 days for the GnRH agonist, the investigators reported.

The optimal ovarian function suppression was seen three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than 001), they added.

One hundred percent of patients receiving degarelix and letrozole maintained optimal ovarian function suppression throughout the study, while about 15% of patients assigned to triptorelin had suboptimal suppression after that first cycle.

The group of patients receiving degarelix had a higher rate of node-negative disease at surgery, and a higher rate of breast-conserving surgery compared with the triptorelin group, the investigators said.

There were two grade 3 adverse events, hypertension and anemia, which both occurred in the triptorelin group, and no grade 4 adverse events. The most common adverse events reported were hot flashes, occurring in 80.0% and 69.2% of the degarelix and triptorelin groups, respectively; arthralgias in 32.0% and 53.8%; insomnia in 24.0% and 11.5%; injection site reactions in 24.0% and 0%; and nausea in 16.0% and 3.8%.

The study was supported by Ferring, and by the International Breast Cancer Study Group via Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland, Oncosuisse, Swiss Cancer League, and the Foundation for Clinical Cancer Research of Eastern Switzerland. The authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.

SOURCE: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. doi: 10.1200/JCO.18.00296.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.

SilverV/thinkstockphotos

The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.

“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.

The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.

That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.

A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–³), and 6.8% of women with no personal cancer history (P less than .001).

Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.

When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).

While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.

“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.

Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
 

SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.

Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.

SilverV/thinkstockphotos

The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.

“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.

The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.

That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.

A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–³), and 6.8% of women with no personal cancer history (P less than .001).

Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.

When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).

While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.

“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.

Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
 

SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.

Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.

SilverV/thinkstockphotos

The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.

“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.

The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.

That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.

A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–³), and 6.8% of women with no personal cancer history (P less than .001).

Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.

When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).

While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.

“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.

Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
 

SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.

Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.

“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”

The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.

“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”

The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.



Drivers and explanatory factors

Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”

“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”

Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.

“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”

The study did not tease out that population, Dr. Kim replied.

Study details

The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).

Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.

However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.

Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.

Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.

The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.

In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.

SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
 

SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.

Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.

“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”

The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.

“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”

The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.



Drivers and explanatory factors

Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”

“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”

Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.

“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”

The study did not tease out that population, Dr. Kim replied.

Study details

The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).

Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.

However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.

Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.

Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.

The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.

In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.

SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
 

SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.

Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.

“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”

The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.

“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”

The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.



Drivers and explanatory factors

Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”

“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”

Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.

“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”

The study did not tease out that population, Dr. Kim replied.

Study details

The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).

Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.

However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.

Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.

Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.

The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.

In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.

SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
 

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.