City of Hope researchers have highlighted race-related differences in tumor response to neoadjuvant endocrine therapy among women with hormone-receptor (HR)-positive breast cancer that suggest the current practice of uniform treatment across races may need to be reassessed.

“We identified that while lower stage cancers in Black women respond very well to endocrine therapy, higher stage cancers in Black women do very poorly in response to endocrine therapy. This suggests a different tumor biology that may impact the treatment we give,” said lead researcher Veronica Jones, assistant professor in City of Hope’s Division of Breast Surgery.

Jones presented the findings at the virtual 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved.

She explained that HR-positive breast cancer accounts for approximately 70% of all breast cancer cases regardless of race, but Black women are more than four times as likely to die from the disease as White women. In spite of this, standard treatment with endocrine therapy is consistent across races and there is limited information about how endocrine therapy resistance might contribute to the mortality disparity seen in Black women.

“The purpose of this study was to examine endocrine therapy in the neoadjuvant setting to begin to understand rates of endocrine resistance in Black and white women,” said Jones.

The research team reviewed National Cancer Database data for 3,521 White and 365 Black/African–American (BAA) women with clinical Stage 1–3 HR-positive breast cancer who received neoadjuvant endocrine therapy prior to breast surgery between 2004 and 2017.

They found that following neoadjuvant endocrine treatment 0.8% of tumors shrunk and were therefore downstaged to stage 0 and 0.9% grew and were upstaged to stage 4. Of note, tumor shrinkage only occurred among women with clinical stage 1 or 2 disease before treatment whereas all but two women upstaged from more advanced disease (stage 2 or higher).

When the researchers looked at the data by race they observed that, compared with White women, BAA women were 1.6 times more likely to present with node positive disease, 1.5 times more likely to have stage 3 disease, and 1.5 times more likely to receive neoadjuvant endocrine therapy for more than 24 weeks.

After taking these differences into account, BAA women were a significant 2.85 times more likely to have their tumors downstaged at the end of neoadjuvant treatment than their White counterparts.

However, BAA women were also significantly more likely than White to have their tumors upstaged.

These results “suggest a dichotomous presentation of HR-positive breast cancer biology in BAA women,” said Jones, adding that “for those who receive neoadjuvant therapy, endocrine therapy alone may not be the best approach in Black women who present with more advanced tumors.”

Jones speculates that the findings may also apply in the adjuvant (post-surgery) setting but says that more work is needed. “This is certainly an area where precision medicine can be beneficial. We need to do a better job distinguishing these tumors based on their genetic profile to identify the best treatments.”

In order to address the question of tumor biology, Jones and colleagues at City of Hope are now using RNA sequencing to look closer at genomic differences in hormone receptor breast cancer across races.

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