By Monica J. Smith

In clinical trials of neoadjuvant chemotherapy, younger women tend to have higher rates of pathologic complete response (pCR), which is linked with a better prognosis. New research, however, finds no difference in pCR in a range of age groups, and similar rates of downstaging in the breast and axilla.

To examine the impact of age on pCR and downstaging, Francys Verdial, MD, MPH—who, at the time of the research, was a fellow at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City—and her colleagues evaluated outcomes on 1,385 women with stage I to III breast cancer who had undergone neoadjuvant chemotherapy. (Dr. Verdial is currently a surgeon at Massachusetts General Hospital, in Boston.)

The researchers stratified the patients into three groups: those aged 40 years and under (300 patients), 41 to 60 (772 patients) and those over 60 (311 patients).

“In the case of triple-negative tumors, we also examined the association of tumor-infiltrating lymphocytes [TILs] in BRCA status with pCR,” Dr. Verdial said in a presentation at the 2021 meeting of the American Society of Breast Surgeons.

The distribution of receptor subtypes was similar across age groups. Patients in the youngest cohort were significantly more likely to have ductal histology, poorly differentiated tumors and BRCA mutations than older patients.

As would be expected, among the entire cohort, pCR was more frequent in patients with HER2-positive or triple-negative tumors than in those with hormone-positive, HER2-negative tumors, but the rate of pCR (34%) did not differ across age groups.

Comparing the rate of pCR by age group across subtype, younger women achieved pCR more frequently among those with triple-negative disease, but there were no differences by age in other subtypes.

“Exploring the potential reasons behind the differences in pCR by age in triple-negative tumors, we looked at BRCA status and TILs in this subgroup, and found young women significantly more likely to have a BRCA mutation compared with women in older age groups,” Dr. Verdial said.

“Among women with a BRCA mutation, 67% of young women had a pCR compared to 44% and 0% of older women. Among those who were BRCA-negative, the rate of pCR did not differ significantly by age.”

Consistent with the literature, women with tumors high in stromal TILs had significantly higher rates of pCR than women without TILs, but stratified by age, the association between TILs and pCR was significant only in the 41- to 60-year-old cohort. “This may be at least partly explained by sample size,” Dr. Verdial said.

After neoadjuvant chemotherapy, about half of the women initially ineligible for breast-conserving surgery became candidates for it, and this conversion rate was seen across all ages. “Despite similar rates of downstaging, however, young women were significantly more likely to opt for bilateral mastectomy than older patients,” Dr. Verdial said.

Downstaging of the axilla after neoadjuvant therapy was higher in women 40 years of age and younger, of whom 94% with biopsy-proven cN1 disease were clinically node-negative after chemotherapy, compared with 89% and 85% in patients aged 41 to 60 and 60 years and older, respectively. More than half of the younger patients (52%) were able to avoid an axillary dissection, compared with 39% and 37% of women in the older cohorts.

Preeti Subhedar, MD, FACS, an assistant professor of surgical oncology at Emory University School of Medicine, in Atlanta, pointed out that even when young women are eligible for breast-conserving surgery, many continue to choose bilateral mastectomy regardless of their response to neoadjuvant chemotherapy.

“The message that overall survival is not different between breast-conserving surgery and mastectomy doesn’t seem to be getting across, especially to younger patients. Maybe we should reframe the conversation; instead of thinking about less treatment, which sounds negative, we should talk about reducing morbidity from procedures they don’t need, which is more positive.”

Dr. Verdial said she’s observed that her surgical colleagues at MSKCC are particularly adept at swaying patients away from larger and potentially more morbid procedures when they are good candidates for breast-conserving surgery.

“I think a lot of it has to do with understanding why the patient is making the decision she’s making, and how you can provide her with the information she needs. This sometimes takes a little extra work, but it’s very important that we understand where patients are coming from, what information they’re using to make their decisions, and what their priorities are,” she said.