Tailoring Treatment for Triple-Negative Breast Cancer in Older Patients

Despite being more commonly diagnosed in women ages 40 or younger, an estimated 10% to 15% of early triple-negative breast cancer (TNBC) cases are diagnosed in patients over 70.

Current guidelines recommend the use of adjuvant chemotherapy in early-stage TNBC regardless of a patient’s age; however, recent data published in JAMA Network Open indicated that underutilization of adjuvant chemotherapy may have contributed to worse outcomes in this patient population in the past.

“When we use these treatments for elderly patients it is a very well-known fact that most of the time we undertreat,” said Ahmed Elkhanany, MD, of Baylor College of Medicine in Houston. “This may lead to a decrease in their outcomes compared with other patients.”

The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results database from 2010 to 2021 to evaluate breast-cancer specific survival of patients ages 70 or older who received chemotherapy compared with those who did not. The analysis included 5,730 women with nonmetastatic TNBC who underwent surgical removal of their cancer.

Of the total study population, 2,509 patients received chemotherapy and 3,221 did not. Compared with those who did not receive adjuvant chemotherapy, receipt of adjuvant chemotherapy was associated with about a 30% lower risk of death from breast cancer (HR 0.69, 95% CI 0.58-0.82) and a 45% lower risk for death overall (HR 0.55, 95% CI 0.49-0.62). Increasing age — 80-89 years and 90 or older — was associated with lower odds of receipt of adjuvant chemotherapy.

“These numbers are massive and put into perspective how instead of helping patients have a better quality of life, undertreating the elderly population can harm them when it comes to [overall survival],” Elkhanany said. In his practice, he incorporates a patient’s functional age rather than chronological age when assessing patients for receipt of adjuvant therapy.

There are some online tools available to aid this decision, he said, but, unfortunately, one that he commonly used, Adjuvant! Online, is no longer available.

Regardless of age, the current standard of care for patients with early TNBC is the regimen established in the KEYNOTE-522 trial: pembrolizumab plus neoadjuvant chemotherapy followed by adjuvant pembrolizumab. Most of the patients treated in the retrospective study were treated prior to this regimen being established.

Several years ago, Iris Zhi, MD, PhD, of NYU Langone Health in New York, presented real-world data looking at outcomes in elderly patients with TNBC who received the KEYNOTE-522 trial regimen.

“The data showed that older patients benefitted from the regimen similarly to their younger counterparts,” Zhi said. There was no difference in the treatment completion rate by age, and the pathologic complete response (pCR) rates were comparable between older and younger patients.

Similarly, data from the Neo-Real/GBECAM-0123 trial also showed no significant difference in the pCR rate between older and younger patients receiving the KEYNOTE-522 regimen.

However, data from these two analyses provided additional evidence that older patients diagnosed with TNBC have a disease biology that is different than their younger counterparts, Zhi said. For example, in Zhi’s study, older patients were more likely to have lobular and other non-ductal histologies. In data from Neo-Real/GBECAM-0123, older patients were more likely to have a lower Ki-67 index and had fewer germline BRCA1/2 mutations.

“Younger patients with TNBC have disease often driven by BRCA mutations and aggressive biology,” Zhi said. “For older patients, the TNBC entity is different from a biology standpoint. For a lot of patients, the disease is more indolent and slow growing.”

However, the takeaway is that more specific data are needed on these older TNBC patients, Zhi said. In fact, she and her colleagues are in the process of publishing some additional research showing that older patients, regardless of having early- or late-stage disease, are severely underrepresented in clinical trials.

“The limited data we have does suggest that older patients benefit similarly to younger patients; however, because they have been so underrepresented in trials, most studies are not able to separately report those outcomes,” Zhi said. “This speaks to an unmet need for this patient population.”

Zhi agreed that until that data exist, treatment approaches should not be based on age, but should instead include a comprehensive geriatric assessment. There are also tools available like a chemo-toxicity calculator that can aid in assessment and predict a patient’s potential chemotherapy toxicity.

“Most importantly,” Zhi said, “there has to be an understanding of the patient’s goals, any caregiver barriers, and financial toxicities.”