Outcome after neoadjuvant chemotherapy in young breast cancer patients: a pooled analysis of individual patient data from eight prospectively randomized controlled trials

Abstract

Young women with breast cancer (BC) have a worse survival partly due to more aggressive tumor characteristics; however, their response to chemotherapy seems better. We investigated to what extent the prognostic factor pathological complete remission (pCR) after neoadjuvant chemotherapy is applicable to young women. 8949 patients with primary BC and follow-up from eight German neoadjuvant trials were included. A subgroup of 1453 patients <40 years was compared with women aged 40-49 and ≥50 years regarding pCR (ypT0 ypN0), as well as disease free survival (DFS), local recurrence free survival (LRFS), distant disease free survival (DDFS), and overall survival (OS) overall, according to pCR status and subtypes defined by hormone-receptor (HR) status and HER2. pCR was strongly associated with age without a clear age cut-off. The pCR rate was significantly higher in the young compared with other age groups (20.9 vs. 17.7 vs. 13.7 %; p < 0.001). This difference was confined to triple-negative breast cancer (TNBC) and HR +/HER2-. DFS, DDFS, LRFS, and OS were significantly worse for young women. Age was independently prognostic for survival in HR +/HER2-, with women <40 years without pCR having a worse DFS compared to their counterparts with pCR. Young women are more likely to achieve pCR after neoadjuvant chemotherapy, especially in HR +/HER2- and TNBC. Age is not an important prognostic factor in TNBC and HR-/HER2 + but is in HR +/HER2-. Young women with a luminal-like BC seem to benefit more from neoadjuvant chemotherapy than older women, which needs to be taken into account.

Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance)

“…The muted chemotherapy response was unlikely because of the Ki67 assay failure to capture highly proliferative tumors, because an independent examination of tumor cell cycle activity with a multigene proliferation score indicated significantly higher expression of cell cycle–dependent genes when the Ki67 was > 10% at 2 to 4 weeks (Figs 4C and 4D). Low chemotherapy responsiveness could reflect the postmenopausal status of the patient cohort, 16 the high ER content of tumors eligible for neoadjuvant endocrine therapy, 17,18 or the use of endocrine therapy before neoadjuvant chemotherapy. However, the latter hypothesis seems unlikely because, unlike prior studies that raised this concern, 19 endocrine therapy was not administered concurrently with chemotherapy.…”

Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426)

“…Lastly, we did not look at long-term outcomes associated with pCR according to race, ethnicity or BMI. Studies that have done this suggest that among women that achieve pCR outcomes such as disease-free survival and overall survival are similar, but disparities persist among women that do not [28,50]. Further research is necessary to tease apart the molecular characteristics and post-neoadjuvant treatment and behavioral/environmental exposures that contribute to these disparities among non-responders.…”

Breast cancer‐specific survival by clinical subtype after 7 years follow‐up of young and elderly women in a nationwide cohort

“…Thus a question has been whether the poor survival among young women is solely due to the more aggressive disease in this age group. Several, mainly smaller, studies have assessed the effect of hormone receptor status on breast cancer‐specific mortality among young women, but only some included subtype information and few were population‐based . Overall, these studies found a higher breast cancer‐specific mortality among young than middle‐aged women, and in some also when adjusting for subtype.…”