Endocrine Therapy Before Surgery Results in Different Outcomes in Black vs. White Women With Breast Cancer, City of Hope-Led Study Finds

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Zen Logsdon
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The results will be presented at the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Sept. 16 to 19, and included in its press program.

LOS ANGELES — A study led by City of Hope, one of the largest cancer research and treatment organizations in the United States, found that Black women with Stage 1 or 2 breast cancer were almost three times more likely than white women to have tumor shrinkage from hormone therapy delivered prior to surgery, yet Black women were more likely than their white counterparts to have worse outcomes when this type of endocrine therapy before surgery was used at a later stage of disease. The results will be presented at the virtual 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Sept. 16 to 19, 2022. 

In more than 70% of all breast cancer cases, tumors have either estrogen or progesterone hormone receptor sensitivity. Hormone receptor-positive breast cancer is usually treated with endocrine therapy, where medicines target the receptors. Yet, even within this breast cancer subgroup, the disease is varied and should not be treated with relative uniformity, noted Veronica Jones, M.D., a breast cancer expert who also studies cancer health disparities at City of Hope. AACR chose to highlight Jones’ data in its press program for the conference.

“Black women are four times more likely than white women to die of hormone receptor-positive breast cancer. While neoadjuvant endocrine therapy appeared to benefit Black women with Stage 1 and 2 breast cancer, our findings suggest that it was not beneficial in Black women with more advanced tumors. This finding may offer insight into its role in the adjuvant setting as well,” said Jones, assistant professor in City of Hope’s Division of Breast Surgery. 

To examine health outcome differences between Black and white women, Jones and colleagues analyzed 3,521 white women and 365 Black women with Stage 1 through 3 hormone receptor-positive breast cancer from the National Cancer Database. They analyzed changes in tumor size and nodal status after neoadjuvant endocrine therapy, which is treatment before surgery, while also considering duration of treatment.

In current medical practice, endocrine treatment failure cannot be predicted; it is detected when the disease recurs. Little is known about the contribution of endocrine therapy resistance to the mortality disparity seen in Black women.

The researchers found that at diagnosis, Black women were 1.6 times more likely to have cancer detected in lymph nodes and 1.5 times more likely to have Stage 3 disease compared to white women. Black women were 1.5 times more likely to receive neoadjuvant endocrine therapy for longer than 24 weeks.

Because the findings suggest different health outcomes in hormone receptor-positive breast cancer in Black women, it exposes an area where precision medicine can be beneficial. City of Hope harnesses leading-edge, genomic-driven insights and highly specialized oncologists to improve patient outcomes and quality of life. The institution is dedicated to reaching diverse, underserved populations so that they have access to precision medicine.

“We need to do a better job distinguishing these tumors based on their genetic profile to identify the best treatments,” Jones said. “In order to address the question of tumor biology, City of Hope is using RNA sequencing to look closer at genomic differences in hormone receptor-positive breast cancer across races.”

These discoveries may help expand the repertoire of targeted therapies available to breast cancer patients, especially for Black women who have been historically underrepresented in clinical trials.

For people with breast cancer now, Jones said, “Recently the CDK4/6 inhibitor abemaciclib has been approved in the adjuvant treatment of locally advanced tumors and should be considered for all women, including Black women with higher-stage breast cancer.”


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The research was supported by City of Hope.

Abstract

Introduction: Black/African American (BAA) women have 4x higher mortality from hormone receptor positive breast cancer (HR+BC) than white women. Despite this disparity, HR+BC across races is treated with relative uniformity: endocrine therapy. Previous studies have focused on the adjuvant setting. We examined use of neoadjuvant endocrine therapy (NET) in BAA and white women in the National Cancer Database (NCDB) and assessed treatment response by race.

Methods: We queried the NCDB for women with clinical Stage 1 through 3 HR+BC treated between the years 2004 and 2017 with NET. Patients receiving neoadjuvant chemotherapy and with unknown surgery or race were excluded. Time between initiation of NET and date of first operation was used to proxy duration of NET. Our primary objective was to compare in BAA and white women changes in tumor size and nodal status after NET, considering duration of treatment. Univariate and multivariable logistic regression was performed.

Results: The final sample included 9,864 white and 1,090 BAA women. BAA women were disproportionately excluded for receipt of neoadjuvant chemotherapy (OR=1.8, 95%CI 1.6-1.9). Sociodemographic variables differed between the two groups with p<0.001, including payor status (12.8% BAA with Medicaid vs 5.2% white), income (33.8% BAA with <$38000 median household income vs 11.9% white), location (73.4% BAA living in metropolitan areas vs 55.4% white) and treatment facility (45.7% and 28.3% BAA at an academic center and community hospital respectively vs 32.7% and 37% white, respectively). Median duration of NET was higher in BAA (128 days) than white women (114 days), p<0.001. After excluding those with unknown pT/N/M, 3,521 white and 365 BAA women were evaluated for NET response. Overall, 0.8% downstaged to pT0 or pTis and 0.9% upstaged to Stage 4 disease. Women downstaged from only clinical Stage 1 or 2 disease, whereas all but two women upstaged from Stage 2 or higher. Compared to white women, BAA women were more likely to present as node positive (OR=1.6, 95%CI 1.3-2.1) or Stage 3 (OR=1.5, 95%CI 1.1-2.0) and be treated with NET for >24 weeks (OR=1.5, 95%CI 1.2-1.8). On multivariate analyses, compared to white women, BAA women were more likely to downstage to pT0/Tis. BAA women who downstaged to pT0/Tis had longer duration of NET than their white counterparts (median 241 vs 167.5 days, respectively); race was a significant predictor of downstaging on multivariate analysis adjusting for duration of NET and clinical stage (OR=2.85, p=0.016 for BAA). Compared to white women, BAA women were more likely to upstage to Stage 4 on multivariate analysis despite being treated longer with NET and controlling for stage at presentation.

Conclusion: This study offers important insight into the heterogeneity of HR+BC biology across races in response to NET. While longer duration of NET appears beneficial for BAA women presenting with lower stage clinical disease, it did not demonstrate benefit in BAA women with higher clinical stage. These findings suggest a dichotomous presentation of HR+BC biology in BAA women.

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About City of Hope
City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. As an independent, National Cancer Institute-designated comprehensive cancer center, City of Hope brings a uniquely integrated model to patients, spanning cancer care, research and development, academics and training, and innovation initiatives. Research and technology developed at City of Hope has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. A leader in bone marrow transplantation and immunotherapy, such as CAR T cell therapy, City of Hope’s personalized treatment protocols help advance cancer care throughout the world.
 
With a goal of expanding access to the latest discoveries and leading-edge care to more patients, families and communities, City of Hope’s growing national system includes its main Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and Cancer Treatment Centers of America. City of Hope’s affiliated family of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, Twitter, YouTube, Instagram and LinkedIn.

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