No abstract

clinicaltrials.gov Identifier: NCT01426880.

The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.

Obesity is associated with an increased risk of breast cancer (BC) and poorer outcome. We assessed the impact of body mass index (BMI) on pathological complete response (pCR), disease-free (DFS), and overall survival (OS), according to BC subtypes in patients with primary BC treated with neoadjuvant chemotherapy. 8,872 patients with primary BC from eight neoadjuvant trials were categorized according to BMI: underweight (<18.5 kg/m(2)), normal weight (18.5 to <25 kg/m(2)), overweight (25 to <30 kg/m(2)), obese (30 to <40 kg/m(2)), and very obese (≥40 kg/m(2)). BC subtypes were defined as luminal-like (ER/PgR-positive and HER2-negative), HER2/luminal (ER/PgR-positive and HER2-positive), HER2-like (ER/PgR-negative and HER2-positive), and triple-negative (TNBC; ER/PgR- and HER2-negative). pCR rate was higher in normal weight patients compared with all other BMI groups (P = 0.003). Mean DFS and OS were shorter in obese (87.3 months, P = 0.014 and 94.9 months, P = 0.001, respectively) and very obese (66.6 months, P < 0.001 and 75.3 months, P < 0.001, respectively) compared with normal weight patients (91.5 and 98.8 months, respectively) which was confirmed by subpopulation treatment effect pattern plot analyses and was consistent in luminal-like and TNBC. No interaction was observed between BMI and pCR. Normal weight patients experienced less non-hematological adverse events (P = 0.002) and were more likely to receive full taxane doses (P < 0.001) compared with all other BMI groups. In multivariable analysis, the dose of taxanes was predictive for pCR (P < 0.001). Higher BMI was associated with lower pCR and a detrimental impact on survival. Normal weight patients had the best compliance to chemotherapy and received the highest taxane doses, which seems to be related with treatment outcomes.

Breast conservation is feasible for clinically multifocal or multicentric breast cancer patients who undergo NACT without worsening LRFS if tumor-free margins can be attained or if patients achieve a pCR.

We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. Clin Cancer Res; 22(23); 5747-54. ©2016 AACR.

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.

RANK ligand (RANKL) is crucial for the development of mouse mammary glands during pregnancy. RANKL functions as a major paracrine effector of the mitogenic action of progesterone in mammary epithelium via its receptor RANK and has a role in expansion and regenerative potential of mammary stem cells. Pharmacologic inhibition of RANKL attenuates the development of mammary carcinoma and inhibits metastatic progression in multiple mouse models. Primary breast carcinoma samples from the neoadjuvant GeparTrio study were analyzed to correlate the expression of human RANK and RANKL with pathological complete response (pCR), disease-free (DFS), and overall (OS) survival. Pre-treatment FFPE core biopsies (n = 601) were analyzed for percentage and intensity of immunohistochemical RANK and RANKL expression. Antibodies against human RANK (N-1H8; Amgen) and human RANKL (M366; Amgen) were used. RANK protein was expressed in 160 (27 %) patients. Increased RANK expression was observed in 14.5 % of patients and correlated with high tumor grade (p < 0.023) and negative hormone receptor (HR) status (p < 0.001). Patients with high RANK expression showed a higher pCR rate (23.0 % vs. 12.6 %, p = 0.010), shorter DFS (p = 0.038), and OS (p = 0.011). However, prognostic and predictive information was not an independent parameter. Only 6 % of samples expressed RANKL, which was not correlated with any clinical features. Higher RANK expression in the primary tumor is associated with a higher sensitivity to chemotherapy, but also a higher risk of relapse and death. Our study provides a basis for further exploration of the antitumor activity of clinical antibodies against RANKL.