Breast Cancer

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

Key clinical point: Higher sugar-sweetened beverages (SSB) consumption after a breast cancer diagnosis was associated with greater breast cancer-specific and all-cause mortality.

Major finding: Compared with no consumption, the risk for breast cancer-specific and all-cause mortality increased with increasing consumption of SSB (P_trend= .001 and .0001, respectively). The consumption of artificially sweetened beverages was not associated with higher breast cancer-specific or all-cause mortality.

Study details: A prospective cohort of 8,863 women with stages I-III breast cancer who completed a validated food frequency questionnaire every 4 years.

Disclosure: This study was supported by the National Institutes of Health, the American Institute for Cancer Research, and the Breast Cancer Research Foundation. Dr. Holmes received grants, personal fees, and nonfinancial support from various sources outside this work. The remaining authors made no disclosures.

Source: Farvid MS et al. Cancer. 2021 May 4. doi: 10.1002/cncr.33461.

Key clinical point: Higher sugar-sweetened beverages (SSB) consumption after a breast cancer diagnosis was associated with greater breast cancer-specific and all-cause mortality.

Major finding: Compared with no consumption, the risk for breast cancer-specific and all-cause mortality increased with increasing consumption of SSB (P_trend= .001 and .0001, respectively). The consumption of artificially sweetened beverages was not associated with higher breast cancer-specific or all-cause mortality.

Study details: A prospective cohort of 8,863 women with stages I-III breast cancer who completed a validated food frequency questionnaire every 4 years.

Disclosure: This study was supported by the National Institutes of Health, the American Institute for Cancer Research, and the Breast Cancer Research Foundation. Dr. Holmes received grants, personal fees, and nonfinancial support from various sources outside this work. The remaining authors made no disclosures.

Source: Farvid MS et al. Cancer. 2021 May 4. doi: 10.1002/cncr.33461.

Key clinical point: Higher sugar-sweetened beverages (SSB) consumption after a breast cancer diagnosis was associated with greater breast cancer-specific and all-cause mortality.

Major finding: Compared with no consumption, the risk for breast cancer-specific and all-cause mortality increased with increasing consumption of SSB (P_trend= .001 and .0001, respectively). The consumption of artificially sweetened beverages was not associated with higher breast cancer-specific or all-cause mortality.

Study details: A prospective cohort of 8,863 women with stages I-III breast cancer who completed a validated food frequency questionnaire every 4 years.

Disclosure: This study was supported by the National Institutes of Health, the American Institute for Cancer Research, and the Breast Cancer Research Foundation. Dr. Holmes received grants, personal fees, and nonfinancial support from various sources outside this work. The remaining authors made no disclosures.

Source: Farvid MS et al. Cancer. 2021 May 4. doi: 10.1002/cncr.33461.

Key clinical point: In older women with stage I hormone receptor (HR)-positive breast cancer, radiation without endocrine therapy does not increase the risk for second breast cancer events (SBCE).

Major finding: Compared with endocrine therapy plus radiotherapy, radiotherapy alone was not associated with a higher risk for SBCE (P = .137), whereas no therapy (standardized hazard ratio [SHR], 3.7; P less than .001) or endocrine therapy (SHR, 2.2; P = .008) alone was associated with higher risk for SBCE.

Study details: A retrospective study of 13,321 women aged 66 years and older with stage I HR-positive breast cancer who underwent breast-conserving surgery between 2007 and 2012.

Disclosures: The study received funding from the Department of Radiation Oncology, NYU School of Medicine. Dr. Deb received personal fees from the NYU School of Medicine. The other authors did not disclose any conflicts of interest.

Source: Gerber NK et al. Int J Radiat Oncol Biol Phys. 2021 May 8. doi: 10.1016/j.ijrobp.2021.04.030.

Key clinical point: In older women with stage I hormone receptor (HR)-positive breast cancer, radiation without endocrine therapy does not increase the risk for second breast cancer events (SBCE).

Major finding: Compared with endocrine therapy plus radiotherapy, radiotherapy alone was not associated with a higher risk for SBCE (P = .137), whereas no therapy (standardized hazard ratio [SHR], 3.7; P less than .001) or endocrine therapy (SHR, 2.2; P = .008) alone was associated with higher risk for SBCE.

Study details: A retrospective study of 13,321 women aged 66 years and older with stage I HR-positive breast cancer who underwent breast-conserving surgery between 2007 and 2012.

Disclosures: The study received funding from the Department of Radiation Oncology, NYU School of Medicine. Dr. Deb received personal fees from the NYU School of Medicine. The other authors did not disclose any conflicts of interest.

Source: Gerber NK et al. Int J Radiat Oncol Biol Phys. 2021 May 8. doi: 10.1016/j.ijrobp.2021.04.030.

Key clinical point: In older women with stage I hormone receptor (HR)-positive breast cancer, radiation without endocrine therapy does not increase the risk for second breast cancer events (SBCE).

Major finding: Compared with endocrine therapy plus radiotherapy, radiotherapy alone was not associated with a higher risk for SBCE (P = .137), whereas no therapy (standardized hazard ratio [SHR], 3.7; P less than .001) or endocrine therapy (SHR, 2.2; P = .008) alone was associated with higher risk for SBCE.

Study details: A retrospective study of 13,321 women aged 66 years and older with stage I HR-positive breast cancer who underwent breast-conserving surgery between 2007 and 2012.

Disclosures: The study received funding from the Department of Radiation Oncology, NYU School of Medicine. Dr. Deb received personal fees from the NYU School of Medicine. The other authors did not disclose any conflicts of interest.

Source: Gerber NK et al. Int J Radiat Oncol Biol Phys. 2021 May 8. doi: 10.1016/j.ijrobp.2021.04.030.

Key clinical point: In patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, BRCA germline-mutated breast cancer, poly (ADP-ribose) polymerase (PARP) inhibitors improve progression-free survival (PFS), overall survival (OS), and tumor response rate.

Major findings: A PARP-containing regimen showed a small advantage in OS (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00) vs. non-PARP regimen. PARP inhibitors improved PFS (hazard ratio, 0.63; P less than .00001) and tumor response rate (66.9% vs. 48.9%). The rate of grade 3 or higher adverse events was not significantly different in the PARP-containing vs. non-PARP regimen.

Study details: A meta-analysis of 5 randomized controlled trials comparing PARP-containing and non-PARP regimens in patients with locally advanced or metastatic breast cancer.

Disclosures: The funding source for this meta-analysis was not identified. Some of the authors received honoraria, research funding, compensation, financial support, consulting fees, and/or grants outside this work. Dr. Redfern is the Principal Investigator on the Brightness trial and served on the advisory board of AstraZeneca and Pfizer.

Source: Taylor AM. Cochrane Database Syst Rev. 2021 Apr 22. doi: 10.1002/14651858.CD011395.pub2.

Key clinical point: In patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, BRCA germline-mutated breast cancer, poly (ADP-ribose) polymerase (PARP) inhibitors improve progression-free survival (PFS), overall survival (OS), and tumor response rate.

Major findings: A PARP-containing regimen showed a small advantage in OS (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00) vs. non-PARP regimen. PARP inhibitors improved PFS (hazard ratio, 0.63; P less than .00001) and tumor response rate (66.9% vs. 48.9%). The rate of grade 3 or higher adverse events was not significantly different in the PARP-containing vs. non-PARP regimen.

Study details: A meta-analysis of 5 randomized controlled trials comparing PARP-containing and non-PARP regimens in patients with locally advanced or metastatic breast cancer.

Disclosures: The funding source for this meta-analysis was not identified. Some of the authors received honoraria, research funding, compensation, financial support, consulting fees, and/or grants outside this work. Dr. Redfern is the Principal Investigator on the Brightness trial and served on the advisory board of AstraZeneca and Pfizer.

Source: Taylor AM. Cochrane Database Syst Rev. 2021 Apr 22. doi: 10.1002/14651858.CD011395.pub2.

Key clinical point: In patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, BRCA germline-mutated breast cancer, poly (ADP-ribose) polymerase (PARP) inhibitors improve progression-free survival (PFS), overall survival (OS), and tumor response rate.

Major findings: A PARP-containing regimen showed a small advantage in OS (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00) vs. non-PARP regimen. PARP inhibitors improved PFS (hazard ratio, 0.63; P less than .00001) and tumor response rate (66.9% vs. 48.9%). The rate of grade 3 or higher adverse events was not significantly different in the PARP-containing vs. non-PARP regimen.

Study details: A meta-analysis of 5 randomized controlled trials comparing PARP-containing and non-PARP regimens in patients with locally advanced or metastatic breast cancer.

Disclosures: The funding source for this meta-analysis was not identified. Some of the authors received honoraria, research funding, compensation, financial support, consulting fees, and/or grants outside this work. Dr. Redfern is the Principal Investigator on the Brightness trial and served on the advisory board of AstraZeneca and Pfizer.

Source: Taylor AM. Cochrane Database Syst Rev. 2021 Apr 22. doi: 10.1002/14651858.CD011395.pub2.

Key clinical point: Fertility concerns affect adjuvant endocrine therapy (ET) decisions in one-third of young breast cancer survivors.

Major finding: Within 2 years after diagnosis, fertility concerns affected ET decisions in 33.12% of women. Parity at diagnosis showed a significant association with fertility concerns. The women who reported that fertility concerns affected their ET decisions showed a higher rate of noninitiation/nonpersistence with ET vs. those without fertility concerns (40% vs. 20%; P less than .0001).

Study details: An analysis of 643 hormone receptor-positive women (mean age, 36 years) who completed a survey from the Young Women’s Breast Cancer Study.

Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Dr. Rosenberg received a grant from the Agency for Healthcare Research and Quality. Dr. Sella was supported by the Pinchas Borenstein Talpiot Medical Leadership Program at Sheba Medical Center and the American Physicians Fellowship for Medicine in Israel. The authors reported receiving honorarium/research funding/consultancy fees/personal fees outside this study work. Dr. Peppercorn reported employment by/stocks in GlaxoSmithKline.

Source: Sella T. Cancer. 2021 Apr 22. doi: 10.1002/cncr.33596.

Key clinical point: Fertility concerns affect adjuvant endocrine therapy (ET) decisions in one-third of young breast cancer survivors.

Major finding: Within 2 years after diagnosis, fertility concerns affected ET decisions in 33.12% of women. Parity at diagnosis showed a significant association with fertility concerns. The women who reported that fertility concerns affected their ET decisions showed a higher rate of noninitiation/nonpersistence with ET vs. those without fertility concerns (40% vs. 20%; P less than .0001).

Study details: An analysis of 643 hormone receptor-positive women (mean age, 36 years) who completed a survey from the Young Women’s Breast Cancer Study.

Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Dr. Rosenberg received a grant from the Agency for Healthcare Research and Quality. Dr. Sella was supported by the Pinchas Borenstein Talpiot Medical Leadership Program at Sheba Medical Center and the American Physicians Fellowship for Medicine in Israel. The authors reported receiving honorarium/research funding/consultancy fees/personal fees outside this study work. Dr. Peppercorn reported employment by/stocks in GlaxoSmithKline.

Source: Sella T. Cancer. 2021 Apr 22. doi: 10.1002/cncr.33596.

Key clinical point: Fertility concerns affect adjuvant endocrine therapy (ET) decisions in one-third of young breast cancer survivors.

Major finding: Within 2 years after diagnosis, fertility concerns affected ET decisions in 33.12% of women. Parity at diagnosis showed a significant association with fertility concerns. The women who reported that fertility concerns affected their ET decisions showed a higher rate of noninitiation/nonpersistence with ET vs. those without fertility concerns (40% vs. 20%; P less than .0001).

Study details: An analysis of 643 hormone receptor-positive women (mean age, 36 years) who completed a survey from the Young Women’s Breast Cancer Study.

Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Dr. Rosenberg received a grant from the Agency for Healthcare Research and Quality. Dr. Sella was supported by the Pinchas Borenstein Talpiot Medical Leadership Program at Sheba Medical Center and the American Physicians Fellowship for Medicine in Israel. The authors reported receiving honorarium/research funding/consultancy fees/personal fees outside this study work. Dr. Peppercorn reported employment by/stocks in GlaxoSmithKline.

Source: Sella T. Cancer. 2021 Apr 22. doi: 10.1002/cncr.33596.

Key clinical point: The risk for breast cancer-specific mortality (BCSM) remains high beyond 5 years. The BCSM rate is significantly higher in hormone receptor (HR)-positive vs. HR-negative women.

Major finding: The overall BCSM rate was 14.9%. Of all BCSM, 54.2% of deaths occurred after 5 years and were significantly higher in HR-positive vs. HR-negative patients (P less than .001). Among patients with HR-positive and HR-negative breast cancer, independent risk factors for BCSM conditional on having survived 5 years were tumor size, nodal status, age, and year of diagnosis. Among patients with HR-positive status, tumor grade, marital status, and race were also independently associated with the risk for BCSM.

Study details: An observational study of 202,080 women with breast cancer with known HR status diagnosed between 1990 and 2005.

Disclosures: The study did not receive any funding. Some authors received research funding and/or advisory/consulting fees from various sources.

Source: Leone JP. Breast Cancer Res Treat. 2021 Apr 24. doi: 10.1007/s10549-021-06233-4.

Key clinical point: The risk for breast cancer-specific mortality (BCSM) remains high beyond 5 years. The BCSM rate is significantly higher in hormone receptor (HR)-positive vs. HR-negative women.

Major finding: The overall BCSM rate was 14.9%. Of all BCSM, 54.2% of deaths occurred after 5 years and were significantly higher in HR-positive vs. HR-negative patients (P less than .001). Among patients with HR-positive and HR-negative breast cancer, independent risk factors for BCSM conditional on having survived 5 years were tumor size, nodal status, age, and year of diagnosis. Among patients with HR-positive status, tumor grade, marital status, and race were also independently associated with the risk for BCSM.

Study details: An observational study of 202,080 women with breast cancer with known HR status diagnosed between 1990 and 2005.

Disclosures: The study did not receive any funding. Some authors received research funding and/or advisory/consulting fees from various sources.

Source: Leone JP. Breast Cancer Res Treat. 2021 Apr 24. doi: 10.1007/s10549-021-06233-4.

Key clinical point: The risk for breast cancer-specific mortality (BCSM) remains high beyond 5 years. The BCSM rate is significantly higher in hormone receptor (HR)-positive vs. HR-negative women.

Major finding: The overall BCSM rate was 14.9%. Of all BCSM, 54.2% of deaths occurred after 5 years and were significantly higher in HR-positive vs. HR-negative patients (P less than .001). Among patients with HR-positive and HR-negative breast cancer, independent risk factors for BCSM conditional on having survived 5 years were tumor size, nodal status, age, and year of diagnosis. Among patients with HR-positive status, tumor grade, marital status, and race were also independently associated with the risk for BCSM.

Study details: An observational study of 202,080 women with breast cancer with known HR status diagnosed between 1990 and 2005.

Disclosures: The study did not receive any funding. Some authors received research funding and/or advisory/consulting fees from various sources.

Source: Leone JP. Breast Cancer Res Treat. 2021 Apr 24. doi: 10.1007/s10549-021-06233-4.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: Immediate reconstruction after neoadjuvant chemotherapy in women with T4 breast cancer is associated with higher odds for complication resulting in unplanned reoperations and a longer time to postmastectomy radiotherapy.

Major finding: Unplanned reoperations for complications were more common after immediate vs. delayed and no reconstruction (22% vs. 7.3% and 4.4%, respectively; P less than .001). The median time to initiation of postmastectomy radiotherapy was longer after immediate reconstruction vs. delayed and no reconstruction (60 days vs. 42 days and 49 days, respectively; P less than .001). The median time to the first recurrence was 18 months and was not significantly different between the groups (P = .13).

Study details: A retrospective study of 269 consecutive women with stage T4 breast cancer treated with surgery, chemotherapy, and radiotherapy between 2007 and 2019.

Disclosure: This study was supported in part by the National Institutes of Health. Dr. Morrow received speaking honoraria from Roche. The other authors did not disclose any conflicts of interest.

Source: Pawloski KR et al. J Am Coll Surg. 2021 Apr 24. doi: 10.1016/j.jamcollsurg.2021.04.016.

Key clinical point: Immediate reconstruction after neoadjuvant chemotherapy in women with T4 breast cancer is associated with higher odds for complication resulting in unplanned reoperations and a longer time to postmastectomy radiotherapy.

Major finding: Unplanned reoperations for complications were more common after immediate vs. delayed and no reconstruction (22% vs. 7.3% and 4.4%, respectively; P less than .001). The median time to initiation of postmastectomy radiotherapy was longer after immediate reconstruction vs. delayed and no reconstruction (60 days vs. 42 days and 49 days, respectively; P less than .001). The median time to the first recurrence was 18 months and was not significantly different between the groups (P = .13).

Study details: A retrospective study of 269 consecutive women with stage T4 breast cancer treated with surgery, chemotherapy, and radiotherapy between 2007 and 2019.

Disclosure: This study was supported in part by the National Institutes of Health. Dr. Morrow received speaking honoraria from Roche. The other authors did not disclose any conflicts of interest.

Source: Pawloski KR et al. J Am Coll Surg. 2021 Apr 24. doi: 10.1016/j.jamcollsurg.2021.04.016.

Key clinical point: Immediate reconstruction after neoadjuvant chemotherapy in women with T4 breast cancer is associated with higher odds for complication resulting in unplanned reoperations and a longer time to postmastectomy radiotherapy.

Major finding: Unplanned reoperations for complications were more common after immediate vs. delayed and no reconstruction (22% vs. 7.3% and 4.4%, respectively; P less than .001). The median time to initiation of postmastectomy radiotherapy was longer after immediate reconstruction vs. delayed and no reconstruction (60 days vs. 42 days and 49 days, respectively; P less than .001). The median time to the first recurrence was 18 months and was not significantly different between the groups (P = .13).

Study details: A retrospective study of 269 consecutive women with stage T4 breast cancer treated with surgery, chemotherapy, and radiotherapy between 2007 and 2019.

Disclosure: This study was supported in part by the National Institutes of Health. Dr. Morrow received speaking honoraria from Roche. The other authors did not disclose any conflicts of interest.

Source: Pawloski KR et al. J Am Coll Surg. 2021 Apr 24. doi: 10.1016/j.jamcollsurg.2021.04.016.

Key clinical point: The presence and extent of coronary artery calcium (CAC), as automatically quantified on routinely performed computed tomography scans, are associated with cardiovascular and coronary artery diseases.

Major finding: The risk for cardiovascular disease increased with a higher CAC score (adjusted hazard ratio, 1.8, 2.1, and 3.4 for CAC scores 11-100, 101-400, and greater than 400, respectively). The risk for coronary artery disease also increased with an increase in CAC score (adjusted hazard ratio, 2.8, 4.3, and 7.8 for CAC scores 11-100, 101-400, and greater than 400, respectively).

Study details: A multicenter cohort study of 15,915 patients with breast cancer who received radiotherapy between 2005 and 2016. The CAC scores were automatically extracted from computed tomography scans using a deep learning algorithm.

Disclosure: This study was funded by the Dutch Cancer Society. The authors received grants, lecture fees, and research support from various sources. Dr. Leiner and Dr. Isgum owned shares of Quantib-U BV and/or a patent with royalties planned. No other conflicts of interest were reported.

Source: Gal R et al. JAMA Oncol. 2021 May 6. doi: 10.1001/jamaoncol.2021.1144.

Key clinical point: The presence and extent of coronary artery calcium (CAC), as automatically quantified on routinely performed computed tomography scans, are associated with cardiovascular and coronary artery diseases.

Major finding: The risk for cardiovascular disease increased with a higher CAC score (adjusted hazard ratio, 1.8, 2.1, and 3.4 for CAC scores 11-100, 101-400, and greater than 400, respectively). The risk for coronary artery disease also increased with an increase in CAC score (adjusted hazard ratio, 2.8, 4.3, and 7.8 for CAC scores 11-100, 101-400, and greater than 400, respectively).

Study details: A multicenter cohort study of 15,915 patients with breast cancer who received radiotherapy between 2005 and 2016. The CAC scores were automatically extracted from computed tomography scans using a deep learning algorithm.

Disclosure: This study was funded by the Dutch Cancer Society. The authors received grants, lecture fees, and research support from various sources. Dr. Leiner and Dr. Isgum owned shares of Quantib-U BV and/or a patent with royalties planned. No other conflicts of interest were reported.

Source: Gal R et al. JAMA Oncol. 2021 May 6. doi: 10.1001/jamaoncol.2021.1144.

Key clinical point: The presence and extent of coronary artery calcium (CAC), as automatically quantified on routinely performed computed tomography scans, are associated with cardiovascular and coronary artery diseases.

Major finding: The risk for cardiovascular disease increased with a higher CAC score (adjusted hazard ratio, 1.8, 2.1, and 3.4 for CAC scores 11-100, 101-400, and greater than 400, respectively). The risk for coronary artery disease also increased with an increase in CAC score (adjusted hazard ratio, 2.8, 4.3, and 7.8 for CAC scores 11-100, 101-400, and greater than 400, respectively).

Study details: A multicenter cohort study of 15,915 patients with breast cancer who received radiotherapy between 2005 and 2016. The CAC scores were automatically extracted from computed tomography scans using a deep learning algorithm.

Disclosure: This study was funded by the Dutch Cancer Society. The authors received grants, lecture fees, and research support from various sources. Dr. Leiner and Dr. Isgum owned shares of Quantib-U BV and/or a patent with royalties planned. No other conflicts of interest were reported.

Source: Gal R et al. JAMA Oncol. 2021 May 6. doi: 10.1001/jamaoncol.2021.1144.