Breast Cancer

Key clinical point: In patients with cT1-2 N0 breast cancer (BC) who underwent mastectomy and had 1-2 positive nodes on sentinel lymph node biopsy (SLNB), the rate of local-regional recurrence (LRR) was extremely low regardless of completion axillary node dissection (CLND) or radiation therapy.

Major finding: The 5-year cumulative incidence rate of overall LRR was comparable between patients who underwent vs did not undergo CLND (1.8% vs 1.3%; P = .93), with the receipt of post-mastectomy radiation therapy not affecting the LRR rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638 for both).

Study details: Findings are from the analysis of a prospective institutional database including 548 patients with cT1-2 N0 BC who underwent mastectomy and had 1-2 positive lymph nodes on SLNB, and 77% of these patients underwent CLND.

Disclosures: This study was supported by the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research and other sources. The authors declared no conflicts of interest.

Source: Zaveri S et al. Extremely low incidence of local-regional recurrences observed among T1-2 N1 (1 or 2 positive SLNs) breast cancer patients receiving upfront mastectomy without completion axillary node dissection. Ann Surg Oncol. 2023 (Jul 17). doi: 10.1245/s10434-023-13942-1

Key clinical point: In patients with cT1-2 N0 breast cancer (BC) who underwent mastectomy and had 1-2 positive nodes on sentinel lymph node biopsy (SLNB), the rate of local-regional recurrence (LRR) was extremely low regardless of completion axillary node dissection (CLND) or radiation therapy.

Major finding: The 5-year cumulative incidence rate of overall LRR was comparable between patients who underwent vs did not undergo CLND (1.8% vs 1.3%; P = .93), with the receipt of post-mastectomy radiation therapy not affecting the LRR rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638 for both).

Study details: Findings are from the analysis of a prospective institutional database including 548 patients with cT1-2 N0 BC who underwent mastectomy and had 1-2 positive lymph nodes on SLNB, and 77% of these patients underwent CLND.

Disclosures: This study was supported by the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research and other sources. The authors declared no conflicts of interest.

Source: Zaveri S et al. Extremely low incidence of local-regional recurrences observed among T1-2 N1 (1 or 2 positive SLNs) breast cancer patients receiving upfront mastectomy without completion axillary node dissection. Ann Surg Oncol. 2023 (Jul 17). doi: 10.1245/s10434-023-13942-1

Key clinical point: In patients with cT1-2 N0 breast cancer (BC) who underwent mastectomy and had 1-2 positive nodes on sentinel lymph node biopsy (SLNB), the rate of local-regional recurrence (LRR) was extremely low regardless of completion axillary node dissection (CLND) or radiation therapy.

Major finding: The 5-year cumulative incidence rate of overall LRR was comparable between patients who underwent vs did not undergo CLND (1.8% vs 1.3%; P = .93), with the receipt of post-mastectomy radiation therapy not affecting the LRR rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638 for both).

Study details: Findings are from the analysis of a prospective institutional database including 548 patients with cT1-2 N0 BC who underwent mastectomy and had 1-2 positive lymph nodes on SLNB, and 77% of these patients underwent CLND.

Disclosures: This study was supported by the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research and other sources. The authors declared no conflicts of interest.

Source: Zaveri S et al. Extremely low incidence of local-regional recurrences observed among T1-2 N1 (1 or 2 positive SLNs) breast cancer patients receiving upfront mastectomy without completion axillary node dissection. Ann Surg Oncol. 2023 (Jul 17). doi: 10.1245/s10434-023-13942-1

Key clinical point: Patients with advanced or metastatic breast cancer (BC) who received concomitant proton pump inhibitors (PPI) plus palbociclib experienced less favorable survival outcomes compared with those who received palbociclib only.

Major finding: Patients who received concomitant PPI + palbociclib vs only palbociclib had significantly shorter progression-free survival (hazard ratio [HR] 1.76; 95% CI 1.46-2.13) and overall survival (HR 2.72; 95% CI 2.07-3.53) rates.

Study details: This retrospective cohort study included 1310 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced or metastatic BC, of which 344 and 966 patients received concomitant PPI + palbociclib and palbociclib only, respectively.

Disclosures: This study was funded by Sungkyunkwan University (South Korea), the Korean Ministry of Education, and the National Research Foundation of Korea. The authors declared no conflicts of interest.

Source: Lee J-E et al. Concomitant use of proton pump inhibitors and palbociclib among patients with breast cancer. JAMA Netw Open. 2023;6(7):e2324852 (Jul 21). doi: 10.1001/jamanetworkopen.2023.24852

Key clinical point: Patients with advanced or metastatic breast cancer (BC) who received concomitant proton pump inhibitors (PPI) plus palbociclib experienced less favorable survival outcomes compared with those who received palbociclib only.

Major finding: Patients who received concomitant PPI + palbociclib vs only palbociclib had significantly shorter progression-free survival (hazard ratio [HR] 1.76; 95% CI 1.46-2.13) and overall survival (HR 2.72; 95% CI 2.07-3.53) rates.

Study details: This retrospective cohort study included 1310 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced or metastatic BC, of which 344 and 966 patients received concomitant PPI + palbociclib and palbociclib only, respectively.

Disclosures: This study was funded by Sungkyunkwan University (South Korea), the Korean Ministry of Education, and the National Research Foundation of Korea. The authors declared no conflicts of interest.

Source: Lee J-E et al. Concomitant use of proton pump inhibitors and palbociclib among patients with breast cancer. JAMA Netw Open. 2023;6(7):e2324852 (Jul 21). doi: 10.1001/jamanetworkopen.2023.24852

Key clinical point: Patients with advanced or metastatic breast cancer (BC) who received concomitant proton pump inhibitors (PPI) plus palbociclib experienced less favorable survival outcomes compared with those who received palbociclib only.

Major finding: Patients who received concomitant PPI + palbociclib vs only palbociclib had significantly shorter progression-free survival (hazard ratio [HR] 1.76; 95% CI 1.46-2.13) and overall survival (HR 2.72; 95% CI 2.07-3.53) rates.

Study details: This retrospective cohort study included 1310 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced or metastatic BC, of which 344 and 966 patients received concomitant PPI + palbociclib and palbociclib only, respectively.

Disclosures: This study was funded by Sungkyunkwan University (South Korea), the Korean Ministry of Education, and the National Research Foundation of Korea. The authors declared no conflicts of interest.

Source: Lee J-E et al. Concomitant use of proton pump inhibitors and palbociclib among patients with breast cancer. JAMA Netw Open. 2023;6(7):e2324852 (Jul 21). doi: 10.1001/jamanetworkopen.2023.24852

Key clinical point: Discontinuing adjuvant hormone therapy (HT) was associated with a higher likelihood of discontinuing cardiovascular therapy and an increased risk for mortality due to cardiovascular diseases in patients with estrogen receptor-positive breast cancer (ER+ BC).

Major finding: Compared with patients who continued adjuvant HT, the rate of discontinuing cardiovascular therapy was higher among patients who discontinued HT within a period of 3 months before (incidence rate ratio [IRR] 1.83; 95% CI 1.41-2.37) and after (IRR 2.31; 95% CI 1.74-3.05) adjuvant HT discontinuation. Discontinuation of adjuvant HT was also associated with a higher risk for death due to cardiovascular diseases (hazard ratio 1.79; 95% CI 1.15-2.81).

Study details: Findings are from a population-based cohort study including 5493 patients with nonmetastatic ER+ BC who initiated adjuvant HT and concomitantly used cardiovascular therapy.

Disclosures: This study was supported by grants from the Swedish Research Council and other sources. The authors declared no conflicts of interest.

Source: He W et al. Concomitant discontinuation of cardiovascular therapy and adjuvant hormone therapy among patients with breast cancer. JAMA Netw Open. 2023;6(7):e2323752 (Jul 17). doi: 10.1001/jamanetworkopen.2023.23752

Key clinical point: Discontinuing adjuvant hormone therapy (HT) was associated with a higher likelihood of discontinuing cardiovascular therapy and an increased risk for mortality due to cardiovascular diseases in patients with estrogen receptor-positive breast cancer (ER+ BC).

Major finding: Compared with patients who continued adjuvant HT, the rate of discontinuing cardiovascular therapy was higher among patients who discontinued HT within a period of 3 months before (incidence rate ratio [IRR] 1.83; 95% CI 1.41-2.37) and after (IRR 2.31; 95% CI 1.74-3.05) adjuvant HT discontinuation. Discontinuation of adjuvant HT was also associated with a higher risk for death due to cardiovascular diseases (hazard ratio 1.79; 95% CI 1.15-2.81).

Study details: Findings are from a population-based cohort study including 5493 patients with nonmetastatic ER+ BC who initiated adjuvant HT and concomitantly used cardiovascular therapy.

Disclosures: This study was supported by grants from the Swedish Research Council and other sources. The authors declared no conflicts of interest.

Source: He W et al. Concomitant discontinuation of cardiovascular therapy and adjuvant hormone therapy among patients with breast cancer. JAMA Netw Open. 2023;6(7):e2323752 (Jul 17). doi: 10.1001/jamanetworkopen.2023.23752

Key clinical point: Discontinuing adjuvant hormone therapy (HT) was associated with a higher likelihood of discontinuing cardiovascular therapy and an increased risk for mortality due to cardiovascular diseases in patients with estrogen receptor-positive breast cancer (ER+ BC).

Major finding: Compared with patients who continued adjuvant HT, the rate of discontinuing cardiovascular therapy was higher among patients who discontinued HT within a period of 3 months before (incidence rate ratio [IRR] 1.83; 95% CI 1.41-2.37) and after (IRR 2.31; 95% CI 1.74-3.05) adjuvant HT discontinuation. Discontinuation of adjuvant HT was also associated with a higher risk for death due to cardiovascular diseases (hazard ratio 1.79; 95% CI 1.15-2.81).

Study details: Findings are from a population-based cohort study including 5493 patients with nonmetastatic ER+ BC who initiated adjuvant HT and concomitantly used cardiovascular therapy.

Disclosures: This study was supported by grants from the Swedish Research Council and other sources. The authors declared no conflicts of interest.

Source: He W et al. Concomitant discontinuation of cardiovascular therapy and adjuvant hormone therapy among patients with breast cancer. JAMA Netw Open. 2023;6(7):e2323752 (Jul 17). doi: 10.1001/jamanetworkopen.2023.23752

Key clinical point: A diagnosis of breast cancer (BC) within the first 5 years of childbirth was associated with aggressive clinicopathological characteristics and unfavorable survival outcomes.

Major finding: Women diagnosed with post-partum BC (PPBC) within 5 years of childbirth showed more aggressive disease characteristics than nulliparous women with BC and women diagnosed with PPBC ≥ 5 years after childbirth (clinical stage T3: 5.9% vs 3.3% and 3.9%, respectively, or higher lymph node metastases: 40.6% vs 27.8% and 34.7%, respectively) and had the worst survival rates (hazard ratio 1.55; P = .004).

Study details: This study retrospectively reviewed 32,628 premenopausal women aged 20-50 years who underwent BC surgery, of which 508 women were nulliparous and 2406 women were diagnosed with BC within 5 years of childbirth.

Disclosures: This study was supported by the Korean Breast Cancer Society. The authors declared no conflicts of interest.

Source: Paik PS et al for the Korean Breast Cancer Society. Clinical characteristics and prognosis of postpartum breast cancer. Breast Cancer Res Treat. 2023 (Aug 5). doi: 10.1007/s10549-023-07069-w

Key clinical point: A diagnosis of breast cancer (BC) within the first 5 years of childbirth was associated with aggressive clinicopathological characteristics and unfavorable survival outcomes.

Major finding: Women diagnosed with post-partum BC (PPBC) within 5 years of childbirth showed more aggressive disease characteristics than nulliparous women with BC and women diagnosed with PPBC ≥ 5 years after childbirth (clinical stage T3: 5.9% vs 3.3% and 3.9%, respectively, or higher lymph node metastases: 40.6% vs 27.8% and 34.7%, respectively) and had the worst survival rates (hazard ratio 1.55; P = .004).

Study details: This study retrospectively reviewed 32,628 premenopausal women aged 20-50 years who underwent BC surgery, of which 508 women were nulliparous and 2406 women were diagnosed with BC within 5 years of childbirth.

Disclosures: This study was supported by the Korean Breast Cancer Society. The authors declared no conflicts of interest.

Source: Paik PS et al for the Korean Breast Cancer Society. Clinical characteristics and prognosis of postpartum breast cancer. Breast Cancer Res Treat. 2023 (Aug 5). doi: 10.1007/s10549-023-07069-w

Key clinical point: A diagnosis of breast cancer (BC) within the first 5 years of childbirth was associated with aggressive clinicopathological characteristics and unfavorable survival outcomes.

Major finding: Women diagnosed with post-partum BC (PPBC) within 5 years of childbirth showed more aggressive disease characteristics than nulliparous women with BC and women diagnosed with PPBC ≥ 5 years after childbirth (clinical stage T3: 5.9% vs 3.3% and 3.9%, respectively, or higher lymph node metastases: 40.6% vs 27.8% and 34.7%, respectively) and had the worst survival rates (hazard ratio 1.55; P = .004).

Study details: This study retrospectively reviewed 32,628 premenopausal women aged 20-50 years who underwent BC surgery, of which 508 women were nulliparous and 2406 women were diagnosed with BC within 5 years of childbirth.

Disclosures: This study was supported by the Korean Breast Cancer Society. The authors declared no conflicts of interest.

Source: Paik PS et al for the Korean Breast Cancer Society. Clinical characteristics and prognosis of postpartum breast cancer. Breast Cancer Res Treat. 2023 (Aug 5). doi: 10.1007/s10549-023-07069-w

Key clinical point: Patients with invasive lobular carcinoma (ILC) of the breast showed worse prognostic outcomes than patients with ILC who also had lobular carcinoma in situ (LCIS).

Major finding: Patients with ILC + LCIS vs ILC only had better median distant recurrence-free survival (DRFS; 16.8 vs 10.1 years; hazard ratio [HR] 0.55; P < .0001) and overall survival (OS; 18.9 vs 13.7 years; HR 0.62; P < .0001) rates, with the absence of LCIS being associated with poor prognosis in terms of both DRFS (adjusted HR 1.78; P < .0001) and OS (adjusted HR 1.60; P < .0001) outcomes.

Study details: This observational, population-based investigation included the data of 4217 patients with stages I-III ILC (of whom 45% had co-existing LCIS) from the MD Anderson breast cancer prospectively collected electronic database.

Disclosures: This study was partly supported by the US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Five authors declared receiving consulting fees or research support from various sources. The other authors declared no conflicts of interest.

Source: Mouabbi JA et al. Absence of lobular carcinoma in situ is a poor prognostic marker in invasive lobular carcinoma. Eur J Cancer. 2023;191:113250 (Jul 21). doi: 10.1016/j.ejca.2023.113250

Key clinical point: Patients with invasive lobular carcinoma (ILC) of the breast showed worse prognostic outcomes than patients with ILC who also had lobular carcinoma in situ (LCIS).

Major finding: Patients with ILC + LCIS vs ILC only had better median distant recurrence-free survival (DRFS; 16.8 vs 10.1 years; hazard ratio [HR] 0.55; P < .0001) and overall survival (OS; 18.9 vs 13.7 years; HR 0.62; P < .0001) rates, with the absence of LCIS being associated with poor prognosis in terms of both DRFS (adjusted HR 1.78; P < .0001) and OS (adjusted HR 1.60; P < .0001) outcomes.

Study details: This observational, population-based investigation included the data of 4217 patients with stages I-III ILC (of whom 45% had co-existing LCIS) from the MD Anderson breast cancer prospectively collected electronic database.

Disclosures: This study was partly supported by the US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Five authors declared receiving consulting fees or research support from various sources. The other authors declared no conflicts of interest.

Source: Mouabbi JA et al. Absence of lobular carcinoma in situ is a poor prognostic marker in invasive lobular carcinoma. Eur J Cancer. 2023;191:113250 (Jul 21). doi: 10.1016/j.ejca.2023.113250

Key clinical point: Patients with invasive lobular carcinoma (ILC) of the breast showed worse prognostic outcomes than patients with ILC who also had lobular carcinoma in situ (LCIS).

Major finding: Patients with ILC + LCIS vs ILC only had better median distant recurrence-free survival (DRFS; 16.8 vs 10.1 years; hazard ratio [HR] 0.55; P < .0001) and overall survival (OS; 18.9 vs 13.7 years; HR 0.62; P < .0001) rates, with the absence of LCIS being associated with poor prognosis in terms of both DRFS (adjusted HR 1.78; P < .0001) and OS (adjusted HR 1.60; P < .0001) outcomes.

Study details: This observational, population-based investigation included the data of 4217 patients with stages I-III ILC (of whom 45% had co-existing LCIS) from the MD Anderson breast cancer prospectively collected electronic database.

Disclosures: This study was partly supported by the US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Five authors declared receiving consulting fees or research support from various sources. The other authors declared no conflicts of interest.

Source: Mouabbi JA et al. Absence of lobular carcinoma in situ is a poor prognostic marker in invasive lobular carcinoma. Eur J Cancer. 2023;191:113250 (Jul 21). doi: 10.1016/j.ejca.2023.113250

Key clinical point: Consumption of alcohol during and 6 months after breast cancer (BC) diagnosis did not negatively impact mortality rates in women who survived BC.

Major finding: The occasional consumption of alcohol (0.36 to < 0.6 g/day) during BC diagnosis (hazard ratio [HR] 0.71; 95% CI 0.54-0.94) and 6 months after BC diagnosis (HR 0.67; 95% CI 0.47-0.94) was associated with a lower risk for all-cause mortality in women with body mass index ≥ 30 kg/m².

Study details: This study analyzed 3659 BC survivors from The Pathways Study (a prospective cohort study) who were diagnosed with stages I-IV invasive BC.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Kwan ML et al. Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study. Cancer. 2023 (Aug 9). doi: 10.1002/cncr.34972

Key clinical point: Consumption of alcohol during and 6 months after breast cancer (BC) diagnosis did not negatively impact mortality rates in women who survived BC.

Major finding: The occasional consumption of alcohol (0.36 to < 0.6 g/day) during BC diagnosis (hazard ratio [HR] 0.71; 95% CI 0.54-0.94) and 6 months after BC diagnosis (HR 0.67; 95% CI 0.47-0.94) was associated with a lower risk for all-cause mortality in women with body mass index ≥ 30 kg/m².

Study details: This study analyzed 3659 BC survivors from The Pathways Study (a prospective cohort study) who were diagnosed with stages I-IV invasive BC.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Kwan ML et al. Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study. Cancer. 2023 (Aug 9). doi: 10.1002/cncr.34972

Key clinical point: Consumption of alcohol during and 6 months after breast cancer (BC) diagnosis did not negatively impact mortality rates in women who survived BC.

Major finding: The occasional consumption of alcohol (0.36 to < 0.6 g/day) during BC diagnosis (hazard ratio [HR] 0.71; 95% CI 0.54-0.94) and 6 months after BC diagnosis (HR 0.67; 95% CI 0.47-0.94) was associated with a lower risk for all-cause mortality in women with body mass index ≥ 30 kg/m².

Study details: This study analyzed 3659 BC survivors from The Pathways Study (a prospective cohort study) who were diagnosed with stages I-IV invasive BC.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Kwan ML et al. Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study. Cancer. 2023 (Aug 9). doi: 10.1002/cncr.34972

Drinking alcohol around the time of a breast cancer diagnosis may not have effects on prognosis that is mediated by body mass index (BMI), an analysis of data from a prospective cohort study suggests.

Kaiser Permanente

The study appears to show that drinking up to one serving of alcohol daily, including wine, beer, and liquor, was not associated with any specific outcomes after breast cancer diagnosis. The authors say these findings could have implications for developing more specific guidelines on alcohol use as it relates to the prevention of death and recurrence for cancer survivors.

Among 3,659 women followed for a mean of 11.2 years after a breast cancer diagnosis, overall alcohol consumption in the months before and up to 6 months after diagnosis was not associated with recurrence or mortality after adjusting for numerous factors such as age at diagnosis, cancer stage, socioeconomic details, smoking history, and preexisting conditions.

However, women with obesity (body mass index of 30 kg/m² or greater) had a lower risk of mortality with increasing alcohol consumption for occasional drinking of 2 or more alcohol servings per week (hazard ratio, 0.71), and regular drinking of at least one alcohol serving daily (HR, 0.77), in a dose-response manner, Marilyn L. Kwan, PhD, and colleagues found.

Dr. Kwan is a senior research scientist at Kaiser Permanente Northern California Division of Research, Oakland.

Women with BMI less than 30 kg/m² did not have a higher risk of mortality but a nonsignificant increase in the risk of recurrence was observed for those who consumed alcohol occasionally (HR, 1.29) and regularly (HR, 1.19), the investigators reported.

The findings were published online in Cancer.

Women included in the current study were participants in the Pathways Study and were diagnosed with stage I-IV breast cancer between 2003 and 2015. During follow-up, 524 recurrences and 834 deaths occurred, including 369 breast cancer-specific deaths, 314 cardiovascular disease-specific deaths, and 151 deaths from other health problems.

Alcohol consumption was assessed for the 6 months prior to cohort entry, which occurred at an average of about 2 months after diagnosis, as well as 6 months later – at an average of about 8 months after diagnosis – using a food-frequency questionnaire.

Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers, the investigators noted.

“This profile appears counterintuitive yet might reflect a healthier lifestyle contributing to better overall survival. Furthermore, higher levels of alcohol consumption could lead to improvement in insulin sensitivity and reduction in insulin-like growth factor-1,” they speculated, noting that reduced fasting insulin concentrations and lower insulin-like growth factor-1 levels are linked with a decreased risk of type 2 diabetes, cardiovascular disease, and cancer.

“Many women with a history of breast cancer are interested in how to improve their prognosis and survival by making lifestyle changes after diagnosis,” they wrote, explaining the rationale for the study. “Current cancer prevention guidelines recommend avoiding alcohol intake or limiting consumption to no more than one drink per day for women. However, no specific guideline exists for cancer survivors other than following the cancer prevention guidelines to reduce the risk of a second cancer.”

High-quality studies on the impact of alcohol consumption on breast cancer prognosis are lacking, they added.

“Given that consuming alcohol is a potentially modifiable lifestyle factor after breast cancer diagnosis, further confirmation is warranted in other large prospective studies of breast cancer survivors with detailed exposure assessment and focus on body size,” they concluded.

The group is the first to report this finding in obese women, and they “strongly believe more research is needed to see if the same association is seen in other studies,” Dr. Kwan told this news organization.

“After a cancer diagnosis, many patients are motivated to make lifestyle changes,” she said. “That often includes adding exercise to their daily routine and eating a healthier diet. Our study findings suggest that doctors can tell patients that having up to a glass of alcohol a day is not likely to increase their risk of a breast cancer recurrence.”

This study was funded by the National Cancer Institute. The authors reported having no disclosures.
 

Drinking alcohol around the time of a breast cancer diagnosis may not have effects on prognosis that is mediated by body mass index (BMI), an analysis of data from a prospective cohort study suggests.

Kaiser Permanente

The study appears to show that drinking up to one serving of alcohol daily, including wine, beer, and liquor, was not associated with any specific outcomes after breast cancer diagnosis. The authors say these findings could have implications for developing more specific guidelines on alcohol use as it relates to the prevention of death and recurrence for cancer survivors.

Among 3,659 women followed for a mean of 11.2 years after a breast cancer diagnosis, overall alcohol consumption in the months before and up to 6 months after diagnosis was not associated with recurrence or mortality after adjusting for numerous factors such as age at diagnosis, cancer stage, socioeconomic details, smoking history, and preexisting conditions.

However, women with obesity (body mass index of 30 kg/m² or greater) had a lower risk of mortality with increasing alcohol consumption for occasional drinking of 2 or more alcohol servings per week (hazard ratio, 0.71), and regular drinking of at least one alcohol serving daily (HR, 0.77), in a dose-response manner, Marilyn L. Kwan, PhD, and colleagues found.

Dr. Kwan is a senior research scientist at Kaiser Permanente Northern California Division of Research, Oakland.

Women with BMI less than 30 kg/m² did not have a higher risk of mortality but a nonsignificant increase in the risk of recurrence was observed for those who consumed alcohol occasionally (HR, 1.29) and regularly (HR, 1.19), the investigators reported.

The findings were published online in Cancer.

Women included in the current study were participants in the Pathways Study and were diagnosed with stage I-IV breast cancer between 2003 and 2015. During follow-up, 524 recurrences and 834 deaths occurred, including 369 breast cancer-specific deaths, 314 cardiovascular disease-specific deaths, and 151 deaths from other health problems.

Alcohol consumption was assessed for the 6 months prior to cohort entry, which occurred at an average of about 2 months after diagnosis, as well as 6 months later – at an average of about 8 months after diagnosis – using a food-frequency questionnaire.

Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers, the investigators noted.

“This profile appears counterintuitive yet might reflect a healthier lifestyle contributing to better overall survival. Furthermore, higher levels of alcohol consumption could lead to improvement in insulin sensitivity and reduction in insulin-like growth factor-1,” they speculated, noting that reduced fasting insulin concentrations and lower insulin-like growth factor-1 levels are linked with a decreased risk of type 2 diabetes, cardiovascular disease, and cancer.

“Many women with a history of breast cancer are interested in how to improve their prognosis and survival by making lifestyle changes after diagnosis,” they wrote, explaining the rationale for the study. “Current cancer prevention guidelines recommend avoiding alcohol intake or limiting consumption to no more than one drink per day for women. However, no specific guideline exists for cancer survivors other than following the cancer prevention guidelines to reduce the risk of a second cancer.”

High-quality studies on the impact of alcohol consumption on breast cancer prognosis are lacking, they added.

“Given that consuming alcohol is a potentially modifiable lifestyle factor after breast cancer diagnosis, further confirmation is warranted in other large prospective studies of breast cancer survivors with detailed exposure assessment and focus on body size,” they concluded.

The group is the first to report this finding in obese women, and they “strongly believe more research is needed to see if the same association is seen in other studies,” Dr. Kwan told this news organization.

“After a cancer diagnosis, many patients are motivated to make lifestyle changes,” she said. “That often includes adding exercise to their daily routine and eating a healthier diet. Our study findings suggest that doctors can tell patients that having up to a glass of alcohol a day is not likely to increase their risk of a breast cancer recurrence.”

This study was funded by the National Cancer Institute. The authors reported having no disclosures.
 

Drinking alcohol around the time of a breast cancer diagnosis may not have effects on prognosis that is mediated by body mass index (BMI), an analysis of data from a prospective cohort study suggests.

Kaiser Permanente

The study appears to show that drinking up to one serving of alcohol daily, including wine, beer, and liquor, was not associated with any specific outcomes after breast cancer diagnosis. The authors say these findings could have implications for developing more specific guidelines on alcohol use as it relates to the prevention of death and recurrence for cancer survivors.

Among 3,659 women followed for a mean of 11.2 years after a breast cancer diagnosis, overall alcohol consumption in the months before and up to 6 months after diagnosis was not associated with recurrence or mortality after adjusting for numerous factors such as age at diagnosis, cancer stage, socioeconomic details, smoking history, and preexisting conditions.

However, women with obesity (body mass index of 30 kg/m² or greater) had a lower risk of mortality with increasing alcohol consumption for occasional drinking of 2 or more alcohol servings per week (hazard ratio, 0.71), and regular drinking of at least one alcohol serving daily (HR, 0.77), in a dose-response manner, Marilyn L. Kwan, PhD, and colleagues found.

Dr. Kwan is a senior research scientist at Kaiser Permanente Northern California Division of Research, Oakland.

Women with BMI less than 30 kg/m² did not have a higher risk of mortality but a nonsignificant increase in the risk of recurrence was observed for those who consumed alcohol occasionally (HR, 1.29) and regularly (HR, 1.19), the investigators reported.

The findings were published online in Cancer.

Women included in the current study were participants in the Pathways Study and were diagnosed with stage I-IV breast cancer between 2003 and 2015. During follow-up, 524 recurrences and 834 deaths occurred, including 369 breast cancer-specific deaths, 314 cardiovascular disease-specific deaths, and 151 deaths from other health problems.

Alcohol consumption was assessed for the 6 months prior to cohort entry, which occurred at an average of about 2 months after diagnosis, as well as 6 months later – at an average of about 8 months after diagnosis – using a food-frequency questionnaire.

Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers, the investigators noted.

“This profile appears counterintuitive yet might reflect a healthier lifestyle contributing to better overall survival. Furthermore, higher levels of alcohol consumption could lead to improvement in insulin sensitivity and reduction in insulin-like growth factor-1,” they speculated, noting that reduced fasting insulin concentrations and lower insulin-like growth factor-1 levels are linked with a decreased risk of type 2 diabetes, cardiovascular disease, and cancer.

“Many women with a history of breast cancer are interested in how to improve their prognosis and survival by making lifestyle changes after diagnosis,” they wrote, explaining the rationale for the study. “Current cancer prevention guidelines recommend avoiding alcohol intake or limiting consumption to no more than one drink per day for women. However, no specific guideline exists for cancer survivors other than following the cancer prevention guidelines to reduce the risk of a second cancer.”

High-quality studies on the impact of alcohol consumption on breast cancer prognosis are lacking, they added.

“Given that consuming alcohol is a potentially modifiable lifestyle factor after breast cancer diagnosis, further confirmation is warranted in other large prospective studies of breast cancer survivors with detailed exposure assessment and focus on body size,” they concluded.

The group is the first to report this finding in obese women, and they “strongly believe more research is needed to see if the same association is seen in other studies,” Dr. Kwan told this news organization.

“After a cancer diagnosis, many patients are motivated to make lifestyle changes,” she said. “That often includes adding exercise to their daily routine and eating a healthier diet. Our study findings suggest that doctors can tell patients that having up to a glass of alcohol a day is not likely to increase their risk of a breast cancer recurrence.”

This study was funded by the National Cancer Institute. The authors reported having no disclosures.
 

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

A version of this article first appeared on WebMD.com.

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

A version of this article first appeared on WebMD.com.

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

A version of this article first appeared on WebMD.com.

TOPLINE:

Most women with breast cancer who received scalp cooling did not perceive benefits in preventing hair loss, overall quality of life, body image, and other outcomes, compared with those who opted to forgo scalp cooling.

METHODOLOGY:

• Although studies have demonstrated the effectiveness of scalp cooling to reduce hair loss during breast cancer chemotherapy, most were in the setting of single-agent regimens instead of much more commonly used combined chemotherapy, and few studies assessed patients’ subjective experience.
• To get a real-world sense of the treatment, investigators compared outcomes in 75 women who opted to use the Orbis Paxman cooling cap during taxane/anthracycline-based chemotherapy sessions with 38 women with breast cancer patients who declined to use the cooling cap.
• The women were surveyed for hair loss perception, functional health, and body image at baseline, midchemotherapy, and at their last chemotherapy cycle, as well as at 3 months and 6-9 months following chemotherapy.
• The women were treated at the Medical University of Innsbruck, Austria, for various stages of breast cancer; about half were premenopausal.

TAKEAWAY:

• There was no significant difference between the scalp-cooling and control groups in patient-reported hair loss (P = .831), overall quality of life (P = .627), emotional functioning (P = .737), social functioning (P = .635), and body image (P = .463).
• On average, women stayed on treatment with the cooling cap for about 40% of the duration of their chemotherapy.
• Overall, 53 of 75 women (70.7%) stopped scalp cooling early, with most (73.9%) citing alopecia as the primary reason; only 30% completed treatment.

IN PRACTICE:

“The efficacy and tolerability of [scalp cooling] applied in a clinical routine setting ... appeared to be limited,” the authors concluded. “The further determination and up-front definition of criteria prognostic for effectiveness of [scalp cooling] may be helpful to identify patient subgroups that may experience a treatment benefit.”

SOURCE:

The work, led by Christine Brunner, Medical University of Innsbruck, Austria, was published in Breast Cancer: Targets and Therapy.

LIMITATIONS:

• Shorter intervals between surveys might have given a more granular understanding of patients’ experiences with scalp cooling.
• There were no biomarker assessments to help identify patients more likely to benefit.

DISCLOSURES:

The work was supported by the Medical University of Innsbruck. Dr. Brunner disclosed a grant from Paxman UK, maker of the cooling cap used in the study. Another investigator disclosed personal fees from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Novartis, and Sirius.

A version of this article first appeared on Medscape.com.

TOPLINE:

Most women with breast cancer who received scalp cooling did not perceive benefits in preventing hair loss, overall quality of life, body image, and other outcomes, compared with those who opted to forgo scalp cooling.

METHODOLOGY:

• Although studies have demonstrated the effectiveness of scalp cooling to reduce hair loss during breast cancer chemotherapy, most were in the setting of single-agent regimens instead of much more commonly used combined chemotherapy, and few studies assessed patients’ subjective experience.
• To get a real-world sense of the treatment, investigators compared outcomes in 75 women who opted to use the Orbis Paxman cooling cap during taxane/anthracycline-based chemotherapy sessions with 38 women with breast cancer patients who declined to use the cooling cap.
• The women were surveyed for hair loss perception, functional health, and body image at baseline, midchemotherapy, and at their last chemotherapy cycle, as well as at 3 months and 6-9 months following chemotherapy.
• The women were treated at the Medical University of Innsbruck, Austria, for various stages of breast cancer; about half were premenopausal.

TAKEAWAY:

• There was no significant difference between the scalp-cooling and control groups in patient-reported hair loss (P = .831), overall quality of life (P = .627), emotional functioning (P = .737), social functioning (P = .635), and body image (P = .463).
• On average, women stayed on treatment with the cooling cap for about 40% of the duration of their chemotherapy.
• Overall, 53 of 75 women (70.7%) stopped scalp cooling early, with most (73.9%) citing alopecia as the primary reason; only 30% completed treatment.

IN PRACTICE:

“The efficacy and tolerability of [scalp cooling] applied in a clinical routine setting ... appeared to be limited,” the authors concluded. “The further determination and up-front definition of criteria prognostic for effectiveness of [scalp cooling] may be helpful to identify patient subgroups that may experience a treatment benefit.”

SOURCE:

The work, led by Christine Brunner, Medical University of Innsbruck, Austria, was published in Breast Cancer: Targets and Therapy.

LIMITATIONS:

• Shorter intervals between surveys might have given a more granular understanding of patients’ experiences with scalp cooling.
• There were no biomarker assessments to help identify patients more likely to benefit.

DISCLOSURES:

The work was supported by the Medical University of Innsbruck. Dr. Brunner disclosed a grant from Paxman UK, maker of the cooling cap used in the study. Another investigator disclosed personal fees from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Novartis, and Sirius.

A version of this article first appeared on Medscape.com.

TOPLINE:

Most women with breast cancer who received scalp cooling did not perceive benefits in preventing hair loss, overall quality of life, body image, and other outcomes, compared with those who opted to forgo scalp cooling.

METHODOLOGY:

• Although studies have demonstrated the effectiveness of scalp cooling to reduce hair loss during breast cancer chemotherapy, most were in the setting of single-agent regimens instead of much more commonly used combined chemotherapy, and few studies assessed patients’ subjective experience.
• To get a real-world sense of the treatment, investigators compared outcomes in 75 women who opted to use the Orbis Paxman cooling cap during taxane/anthracycline-based chemotherapy sessions with 38 women with breast cancer patients who declined to use the cooling cap.
• The women were surveyed for hair loss perception, functional health, and body image at baseline, midchemotherapy, and at their last chemotherapy cycle, as well as at 3 months and 6-9 months following chemotherapy.
• The women were treated at the Medical University of Innsbruck, Austria, for various stages of breast cancer; about half were premenopausal.

TAKEAWAY:

• There was no significant difference between the scalp-cooling and control groups in patient-reported hair loss (P = .831), overall quality of life (P = .627), emotional functioning (P = .737), social functioning (P = .635), and body image (P = .463).
• On average, women stayed on treatment with the cooling cap for about 40% of the duration of their chemotherapy.
• Overall, 53 of 75 women (70.7%) stopped scalp cooling early, with most (73.9%) citing alopecia as the primary reason; only 30% completed treatment.

IN PRACTICE:

“The efficacy and tolerability of [scalp cooling] applied in a clinical routine setting ... appeared to be limited,” the authors concluded. “The further determination and up-front definition of criteria prognostic for effectiveness of [scalp cooling] may be helpful to identify patient subgroups that may experience a treatment benefit.”

SOURCE:

The work, led by Christine Brunner, Medical University of Innsbruck, Austria, was published in Breast Cancer: Targets and Therapy.

LIMITATIONS:

• Shorter intervals between surveys might have given a more granular understanding of patients’ experiences with scalp cooling.
• There were no biomarker assessments to help identify patients more likely to benefit.

DISCLOSURES:

The work was supported by the Medical University of Innsbruck. Dr. Brunner disclosed a grant from Paxman UK, maker of the cooling cap used in the study. Another investigator disclosed personal fees from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Novartis, and Sirius.

A version of this article first appeared on Medscape.com.

Treatment options for patients with cancer that is detected at a late stage are severely limited, which usually leads to an unfavorable prognosis for such patients. Indeed, the options available for patients with metastatic solid cancers are scarcely curative. Therefore, early diagnosis of neoplasia remains a fundamental mainstay for improving outcomes for cancer patients.

Histopathology is the current gold standard for cancer diagnosis. Biopsy is an invasive procedure that provides physicians with further samples to test but that furnishes limited information concerning tumor heterogeneity. Biopsy specimens are usually obtained only when there is clinical evidence of neoplasia, which significantly limits their usefulness in early diagnosis.

Around 20 years ago, it was discovered that the presence of circulating tumor cells (CTC) in patients with metastatic breast cancer who were about to begin a new line of treatment was predictive of overall and progression-free survival. The prognostic value of CTC was independent of the line of treatment (first or second) and was greater than that of the site of metastasis, the type of therapy, and the time to metastasis after complete primary resection. These results support the idea that the presence of CTC could be used to modify the system for staging advanced disease.

Since then, research into liquid biopsy assays has expanded rapidly, and many biomarkers have been studied in various body fluids for their usefulness in assessing solid tumors.
 

Liquid vs. tissue

Liquid biopsy is a minimally invasive tool that is easy to use. It is employed to detect cancer, to assess treatment response, or to monitor disease progression. Liquid biopsy produces test material from primary and metastatic (or micrometastatic) sites and provides a more heterogeneous picture of the entire tumor cell population, compared with specimens obtained with tissue biopsy.

Metastasis

The notion that metastatic lesions are formed from cancer cells that have disseminated from advanced primary tumors has been substantially revised following the identification of disseminated tumor cells (DTC) in the bone marrow of patients with early-stage disease. These results have led researchers to no longer view cancer metastasis as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as metastasizing cells assume new phenotypes while abandoning older behaviors.

The initiation of metastasis is not simply a cell-autonomous event but is heavily influenced by complex tissue microenvironments. Although colonization of distant tissues by DTC is an extremely inefficient process, at times, relatively numerous CTC can be detected in the blood of cancer patients (> 1,000 CTC/mL of blood plasma), whereas the number of clinically detectable metastases is disproportionately low, confirming that tumor cell diffusion can happen at an early stage but usually occurs later on.
 

Early dissemination

Little is currently known about the preference of cancer subtypes for distinct tissues or about the receptiveness of a tissue as a metastatic site. What endures as one of the most confounding clinical phenomena is that patients may undergo tumor resection and remain apparently disease free for months, years, and even decades, only to experience relapse and be diagnosed with late-stage metastatic disease. This course may be a result of cell seeding from minimal residual disease after resection of the primary tumor or of preexisting clinically undetectable micrometastases. It may also arise from early disseminated cells that remain dormant and resistant to therapy until they suddenly reawaken to initiate proliferation into clinically detectable macrometastases.

Dormant DTC could be the main reason for delayed detection of metastases. It is thought that around 40% of patients with prostate cancer who undergo radical prostatectomy present with biochemical recurrence, suggesting that it is likely that hidden DTC or micrometastases are present at the time of the procedure. The finding is consistent with the detection of DTC many years after tumor resection, suggesting they were released before surgical treatment. Nevertheless, research into tumor cell dormancy is limited, owing to the invasive and technically challenging nature of obtaining DTC samples, which are predominantly taken from the bone marrow.
 

CTC metastases

Cancer cells can undergo epithelial-to-mesenchymal transition to facilitate their detachment from the primary tumor and intravasation into the blood circulation (step 1). Dissemination of cancer cells from the primary tumor into circulation can involve either single cells or cell clusters containing multiple CTC as well as immune cells and platelets, known as microemboli. CTC that can survive in circulation (step 2) can exit the bloodstream (step 3) and establish metastatic tumors (step 4), or they can enter dormancy and reside in distant organs, such as the bone marrow.

Use in practice

CTC were discovered over a century ago, but only in recent years has technology been sufficiently advanced to study CTC and to assess their usefulness as biomarkers. Recent evidence suggests that not only do the number of CTC increase during sleep and rest phases but also that these CTC are better able to metastasize, compared to those generated during periods of wakefulness or activity.

CTC clusters (microemboli) are defined as groups of two or more CTC. They can consist of CTC alone (homotypic) or can include various stromal cells, such as cancer-associated fibroblasts or platelets and immune cells (heterotypic). CTC clusters (with or without leukocytes) seem to have greater metastatic capacity, compared with individual CTC.

A multitude of characteristics can be measured in CTC, including genetics and epigenetics, as well as protein levels, which might help in understanding many processes involved in the formation of metastases.

Quantitative assessment of CTC could indicate tumor burden in patients with aggressive cancers, as has been seen in patients with primary lung cancer.
 

Early cancer diagnosis

Early research into CTC didn’t explore their usefulness in diagnosing early-stage tumors because it was thought that CTC were characteristic of advanced-stage disease. This hypothesis was later rejected following evidence of local intravascular invasion of very early cancer cells, even over a period of several hours. This feature may allow CTC to be detected before the clinical diagnosis of cancer.

CTC have been detected in various neoplastic conditions: in breast cancer, seen in 20% of patients with stage I disease, in 26.8% with stage II disease, and 26.7% with stage III disease; in nonmetastatic colorectal cancer, including stage I and II disease; and in prostate cancer, seen in over 50% of patients with localized disease.

The presence of CTC has been proven to be an unfavorable prognostic predictor of overall survival among patients with early-stage non–small cell lung cancer. It distinguishes patients with pancreatic ductal adenocarcinoma from those with noncancerous pancreatic diseases with a sensitivity of 75% and a specificity of 96.3%.

CTC positivity scoring (appropriately defined), combined with serum prostate-specific antigen level, was predictive of a biopsy diagnosis of clinically significant prostate cancer.

All these data support the utility of CTC in early cancer diagnosis. Their link with metastases, and thus with aggressive tumors, gives them an advantage over other (noninvasive or minimally invasive) biomarkers in the early identification of invasive tumors for therapeutic intervention with better cure rates.
 

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Treatment options for patients with cancer that is detected at a late stage are severely limited, which usually leads to an unfavorable prognosis for such patients. Indeed, the options available for patients with metastatic solid cancers are scarcely curative. Therefore, early diagnosis of neoplasia remains a fundamental mainstay for improving outcomes for cancer patients.

Histopathology is the current gold standard for cancer diagnosis. Biopsy is an invasive procedure that provides physicians with further samples to test but that furnishes limited information concerning tumor heterogeneity. Biopsy specimens are usually obtained only when there is clinical evidence of neoplasia, which significantly limits their usefulness in early diagnosis.

Around 20 years ago, it was discovered that the presence of circulating tumor cells (CTC) in patients with metastatic breast cancer who were about to begin a new line of treatment was predictive of overall and progression-free survival. The prognostic value of CTC was independent of the line of treatment (first or second) and was greater than that of the site of metastasis, the type of therapy, and the time to metastasis after complete primary resection. These results support the idea that the presence of CTC could be used to modify the system for staging advanced disease.

Since then, research into liquid biopsy assays has expanded rapidly, and many biomarkers have been studied in various body fluids for their usefulness in assessing solid tumors.
 

Liquid vs. tissue

Liquid biopsy is a minimally invasive tool that is easy to use. It is employed to detect cancer, to assess treatment response, or to monitor disease progression. Liquid biopsy produces test material from primary and metastatic (or micrometastatic) sites and provides a more heterogeneous picture of the entire tumor cell population, compared with specimens obtained with tissue biopsy.

Metastasis

The notion that metastatic lesions are formed from cancer cells that have disseminated from advanced primary tumors has been substantially revised following the identification of disseminated tumor cells (DTC) in the bone marrow of patients with early-stage disease. These results have led researchers to no longer view cancer metastasis as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as metastasizing cells assume new phenotypes while abandoning older behaviors.

The initiation of metastasis is not simply a cell-autonomous event but is heavily influenced by complex tissue microenvironments. Although colonization of distant tissues by DTC is an extremely inefficient process, at times, relatively numerous CTC can be detected in the blood of cancer patients (> 1,000 CTC/mL of blood plasma), whereas the number of clinically detectable metastases is disproportionately low, confirming that tumor cell diffusion can happen at an early stage but usually occurs later on.
 

Early dissemination

Little is currently known about the preference of cancer subtypes for distinct tissues or about the receptiveness of a tissue as a metastatic site. What endures as one of the most confounding clinical phenomena is that patients may undergo tumor resection and remain apparently disease free for months, years, and even decades, only to experience relapse and be diagnosed with late-stage metastatic disease. This course may be a result of cell seeding from minimal residual disease after resection of the primary tumor or of preexisting clinically undetectable micrometastases. It may also arise from early disseminated cells that remain dormant and resistant to therapy until they suddenly reawaken to initiate proliferation into clinically detectable macrometastases.

Dormant DTC could be the main reason for delayed detection of metastases. It is thought that around 40% of patients with prostate cancer who undergo radical prostatectomy present with biochemical recurrence, suggesting that it is likely that hidden DTC or micrometastases are present at the time of the procedure. The finding is consistent with the detection of DTC many years after tumor resection, suggesting they were released before surgical treatment. Nevertheless, research into tumor cell dormancy is limited, owing to the invasive and technically challenging nature of obtaining DTC samples, which are predominantly taken from the bone marrow.
 

CTC metastases

Cancer cells can undergo epithelial-to-mesenchymal transition to facilitate their detachment from the primary tumor and intravasation into the blood circulation (step 1). Dissemination of cancer cells from the primary tumor into circulation can involve either single cells or cell clusters containing multiple CTC as well as immune cells and platelets, known as microemboli. CTC that can survive in circulation (step 2) can exit the bloodstream (step 3) and establish metastatic tumors (step 4), or they can enter dormancy and reside in distant organs, such as the bone marrow.

Use in practice

CTC were discovered over a century ago, but only in recent years has technology been sufficiently advanced to study CTC and to assess their usefulness as biomarkers. Recent evidence suggests that not only do the number of CTC increase during sleep and rest phases but also that these CTC are better able to metastasize, compared to those generated during periods of wakefulness or activity.

CTC clusters (microemboli) are defined as groups of two or more CTC. They can consist of CTC alone (homotypic) or can include various stromal cells, such as cancer-associated fibroblasts or platelets and immune cells (heterotypic). CTC clusters (with or without leukocytes) seem to have greater metastatic capacity, compared with individual CTC.

A multitude of characteristics can be measured in CTC, including genetics and epigenetics, as well as protein levels, which might help in understanding many processes involved in the formation of metastases.

Quantitative assessment of CTC could indicate tumor burden in patients with aggressive cancers, as has been seen in patients with primary lung cancer.
 

Early cancer diagnosis

Early research into CTC didn’t explore their usefulness in diagnosing early-stage tumors because it was thought that CTC were characteristic of advanced-stage disease. This hypothesis was later rejected following evidence of local intravascular invasion of very early cancer cells, even over a period of several hours. This feature may allow CTC to be detected before the clinical diagnosis of cancer.

CTC have been detected in various neoplastic conditions: in breast cancer, seen in 20% of patients with stage I disease, in 26.8% with stage II disease, and 26.7% with stage III disease; in nonmetastatic colorectal cancer, including stage I and II disease; and in prostate cancer, seen in over 50% of patients with localized disease.

The presence of CTC has been proven to be an unfavorable prognostic predictor of overall survival among patients with early-stage non–small cell lung cancer. It distinguishes patients with pancreatic ductal adenocarcinoma from those with noncancerous pancreatic diseases with a sensitivity of 75% and a specificity of 96.3%.

CTC positivity scoring (appropriately defined), combined with serum prostate-specific antigen level, was predictive of a biopsy diagnosis of clinically significant prostate cancer.

All these data support the utility of CTC in early cancer diagnosis. Their link with metastases, and thus with aggressive tumors, gives them an advantage over other (noninvasive or minimally invasive) biomarkers in the early identification of invasive tumors for therapeutic intervention with better cure rates.
 

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Treatment options for patients with cancer that is detected at a late stage are severely limited, which usually leads to an unfavorable prognosis for such patients. Indeed, the options available for patients with metastatic solid cancers are scarcely curative. Therefore, early diagnosis of neoplasia remains a fundamental mainstay for improving outcomes for cancer patients.

Histopathology is the current gold standard for cancer diagnosis. Biopsy is an invasive procedure that provides physicians with further samples to test but that furnishes limited information concerning tumor heterogeneity. Biopsy specimens are usually obtained only when there is clinical evidence of neoplasia, which significantly limits their usefulness in early diagnosis.

Around 20 years ago, it was discovered that the presence of circulating tumor cells (CTC) in patients with metastatic breast cancer who were about to begin a new line of treatment was predictive of overall and progression-free survival. The prognostic value of CTC was independent of the line of treatment (first or second) and was greater than that of the site of metastasis, the type of therapy, and the time to metastasis after complete primary resection. These results support the idea that the presence of CTC could be used to modify the system for staging advanced disease.

Since then, research into liquid biopsy assays has expanded rapidly, and many biomarkers have been studied in various body fluids for their usefulness in assessing solid tumors.
 

Liquid vs. tissue

Liquid biopsy is a minimally invasive tool that is easy to use. It is employed to detect cancer, to assess treatment response, or to monitor disease progression. Liquid biopsy produces test material from primary and metastatic (or micrometastatic) sites and provides a more heterogeneous picture of the entire tumor cell population, compared with specimens obtained with tissue biopsy.

Metastasis

The notion that metastatic lesions are formed from cancer cells that have disseminated from advanced primary tumors has been substantially revised following the identification of disseminated tumor cells (DTC) in the bone marrow of patients with early-stage disease. These results have led researchers to no longer view cancer metastasis as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as metastasizing cells assume new phenotypes while abandoning older behaviors.

The initiation of metastasis is not simply a cell-autonomous event but is heavily influenced by complex tissue microenvironments. Although colonization of distant tissues by DTC is an extremely inefficient process, at times, relatively numerous CTC can be detected in the blood of cancer patients (> 1,000 CTC/mL of blood plasma), whereas the number of clinically detectable metastases is disproportionately low, confirming that tumor cell diffusion can happen at an early stage but usually occurs later on.
 

Early dissemination

Little is currently known about the preference of cancer subtypes for distinct tissues or about the receptiveness of a tissue as a metastatic site. What endures as one of the most confounding clinical phenomena is that patients may undergo tumor resection and remain apparently disease free for months, years, and even decades, only to experience relapse and be diagnosed with late-stage metastatic disease. This course may be a result of cell seeding from minimal residual disease after resection of the primary tumor or of preexisting clinically undetectable micrometastases. It may also arise from early disseminated cells that remain dormant and resistant to therapy until they suddenly reawaken to initiate proliferation into clinically detectable macrometastases.

Dormant DTC could be the main reason for delayed detection of metastases. It is thought that around 40% of patients with prostate cancer who undergo radical prostatectomy present with biochemical recurrence, suggesting that it is likely that hidden DTC or micrometastases are present at the time of the procedure. The finding is consistent with the detection of DTC many years after tumor resection, suggesting they were released before surgical treatment. Nevertheless, research into tumor cell dormancy is limited, owing to the invasive and technically challenging nature of obtaining DTC samples, which are predominantly taken from the bone marrow.
 

CTC metastases

Cancer cells can undergo epithelial-to-mesenchymal transition to facilitate their detachment from the primary tumor and intravasation into the blood circulation (step 1). Dissemination of cancer cells from the primary tumor into circulation can involve either single cells or cell clusters containing multiple CTC as well as immune cells and platelets, known as microemboli. CTC that can survive in circulation (step 2) can exit the bloodstream (step 3) and establish metastatic tumors (step 4), or they can enter dormancy and reside in distant organs, such as the bone marrow.

Use in practice

CTC were discovered over a century ago, but only in recent years has technology been sufficiently advanced to study CTC and to assess their usefulness as biomarkers. Recent evidence suggests that not only do the number of CTC increase during sleep and rest phases but also that these CTC are better able to metastasize, compared to those generated during periods of wakefulness or activity.

CTC clusters (microemboli) are defined as groups of two or more CTC. They can consist of CTC alone (homotypic) or can include various stromal cells, such as cancer-associated fibroblasts or platelets and immune cells (heterotypic). CTC clusters (with or without leukocytes) seem to have greater metastatic capacity, compared with individual CTC.

A multitude of characteristics can be measured in CTC, including genetics and epigenetics, as well as protein levels, which might help in understanding many processes involved in the formation of metastases.

Quantitative assessment of CTC could indicate tumor burden in patients with aggressive cancers, as has been seen in patients with primary lung cancer.
 

Early cancer diagnosis

Early research into CTC didn’t explore their usefulness in diagnosing early-stage tumors because it was thought that CTC were characteristic of advanced-stage disease. This hypothesis was later rejected following evidence of local intravascular invasion of very early cancer cells, even over a period of several hours. This feature may allow CTC to be detected before the clinical diagnosis of cancer.

CTC have been detected in various neoplastic conditions: in breast cancer, seen in 20% of patients with stage I disease, in 26.8% with stage II disease, and 26.7% with stage III disease; in nonmetastatic colorectal cancer, including stage I and II disease; and in prostate cancer, seen in over 50% of patients with localized disease.

The presence of CTC has been proven to be an unfavorable prognostic predictor of overall survival among patients with early-stage non–small cell lung cancer. It distinguishes patients with pancreatic ductal adenocarcinoma from those with noncancerous pancreatic diseases with a sensitivity of 75% and a specificity of 96.3%.

CTC positivity scoring (appropriately defined), combined with serum prostate-specific antigen level, was predictive of a biopsy diagnosis of clinically significant prostate cancer.

All these data support the utility of CTC in early cancer diagnosis. Their link with metastases, and thus with aggressive tumors, gives them an advantage over other (noninvasive or minimally invasive) biomarkers in the early identification of invasive tumors for therapeutic intervention with better cure rates.
 

This article was translated from Univadis Italy. A version appeared on Medscape.com.