Predicting Chemotherapy Benefit in Patients With Breast Cancer With Positive Lymph Nodes Who Are Postmenopausal, Premenopausal

In 2022, it was estimated that there were 287,850 new breast cancer cases diagnosed, 93% of which were early-stage breast cancers, explained Jordan Hill, PharmD, BCOP, during a presentation at the HOPA Annual Conference 2023. Additionally, the 5-year survival of early-stage breast cancer is very high, and the overall death rate from breast cancer has decreased by 43% in the past 30 years, mostly attributed to improvements in screening and management.

Expert presents Updates in Early-Stage Breast Cancer from the HOPA 2023 Annual Conference. Credit: okrasiuk - stock.adobe.com.

There are 3 primary subtypes of breast cancer, the most common of which is hormone receptor-positive (HR+) or human epidermal growth factor receptor 2 negative (HER2-) breast cancers, representing approximately 70% of all cases, followed by HER2-positive (HER2+), which represents 14%. Lastly, triple-negative breast cancer (TNBC) represents 10%, according to Hill.

“Depending on the receptor type, it can significantly impact someone's prognosis,” Hill said. “Patients that have hormone negative cancers are significantly more likely to have recurrences. These recurrences are more likely to happen early within the first 3 to 4 years depending on whether it is HER2+ or not. Alternatively, HR+ cancers…have a much lower risk of recurrence, although that recurrence rate does stay fairly consistent for several years after initial diagnosis. This is important to keep in mind when looking at trials evaluating additional adjuvant treatments for some of these HR+ cancers.”

In addition to varying prognoses based on receptor type, there are certain populations who also have differing prognosis, such as African American patients, who have an earlier onset of breast cancer and are more likely to have an aggressive tumor type, such as TNBC, with shorter survival. The etiology is most likely multifactorial, including socioeconomic, environmental, and genomic factors.

TP53 and BRCA mutations occur more often in this patient population, and actual mutations such as the PIK3CA mutations occur less often. Notably, even after controlling for prognostic factors and socioeconomic factors, mortality differences do still persist, according to Hill.

In the RxPONDER trial (NCT01272037), investigators looked more closely at this difference. They observed that non-Hispanic Black patients, as well as Hispanic patients, were more likely to have high grade tumors. Additionally, after adjusting for normal prognostic factors, such as age, menopausal status, grade, treatment arm, and recurrence score, non-Hispanic Black patients had a worse invasive disease-free survival.

The RxPONDER trial had looked to advance upon prior research that assessed the ability to predict chemotherapy benefit in node-negative patients by assessing responses in patients who had small numbers of positive lymph nodes.

“These patients were HR+, they could be either pre- or post-menopausal, they had to have a low oncotype score, because we know if they had a high one, we would already know they would benefit from chemotherapy, and a limited number of positive lymph nodes, so 1 to 3,” Hill said. “Then they were randomized to either chemo-endocrine therapy or endocrine therapy alone.”

Approximately two-thirds of the patients in the RxPONDER trial were postmenopausal. Additionally, the majority of patients had only 1 lymph node involved, with less than 10% of patients having 3 or more lymph nodes involved.

“What they found was that in the postmenopausal cohort of patients, there wasn't a benefit to adding chemotherapy even if you did have a limited number of nodes involved,” Hill said. “However, alternatively, in our premenopausal patients, that was not the case, as there was significant improvement in both invasive disease-free survival as well as distant-disease-free survival if the patients received chemotherapy versus if they did not.”

Based on the results of the RxPONDER trial, investigators found that premenopausal patients with 1 to 3 lymph nodes involved do, in fact, benefit from the addition of chemotherapy and should receive both chemotherapy and endocrine therapy. However, if patients are node-negative and premenopausal, or if they are postmenopausal with 0 to 3 lymph nodes involved, the Oncotype DX score can be primarily used for recurrence assessment.

“The exception to that is that oncotype 16 to 25 in the patients who are less than or equal to 50 years,” Hill said.

Reference

Hill J. Updates in Early-Stage Breast Cancer. Presented at HOPA Annual Conference 2023 in Phoenix, AZ; March 30, 2023.