Neo-Family History Score is a Novel Biomarker of Pathological Complete Response, Safety, and Survival Outcomes in Patients with Breast Cancer Receiving Neoadjuvant Platinum-Based Chemotherapy: A Retrospective Analysis of Two Prospective Trials

Abstract

Background: Homologous recombination repair gene mutations are associated with increased platinum-based chemosensitivity, whereas few studies have reported the predictive value of family history of cancer for breast cancer in the neoadjuvant setting. This study aimed to construct a brief and effective novel family history scoring system and explore its association with pathological complete response (pCR), survival outcomes, and safety for locally advanced breast cancer receiving platinum-based neoadjuvant chemotherapy.

Methods: A total of 262 patients treated with neoadjuvant cisplatin and paclitaxel were included. Neo-Family History Score (NeoFHS) was calculated according to cancer type, age at diagnosis, kinship, and number of affected relatives. Logistic regression was performed to analyze the association between pCR and NeoFHS. Survival rates were compared by Kaplan-Meier curves, examined by log-rank test and Cox proportional hazard regressions.

Results: For all patients enrolled in this study, clinical tumor stage (p=0·048), estrogen receptor status (p=0·001), progesterone receptor status (p=0·036), human epidermal growth factor receptor 2 (HER2) status (p=0·013), and molecular subtype (p=0·016) were significantly related to NeoFHS. The multivariate logistic regression revealed that NeoFHS is an independent predictive factor of pCR (OR=2·262, 95% CI 1·159-4·414, p=0·017), especially in node-positive (OR=3·088, 95% CI 1·498-6·367, p=0·002), hormone receptor-positive (OR=2·645, 95% CI 1·164-6·010, p=0·020), and HER2-negative subgroups (OR=4·786, 95% CI 1·550-14·775, p=0·006). Kaplan-Meier estimates suggested that NeoFHS could serve as an independent prognostic factor for relapse-free survival in the whole group (adjusted HR=0·305, 95% CI 0·102-0·910, p=0·033) and node-positive subgroup (adjusted HR=0·317, 95% CI 0·103-0·973, p=0·045). Furthermore, alopecia (p=0·001), nausea (p=0·001), peripheral neuropathy (p=0·018), diarrhea (p=0·026), constipation (p=0·037) of any grade and leukopenia of grade 3 or greater (p=0·005) were more common in patients with higher NeoFHS.

Conclusions: Our study revealed that NeoFHS is a practical and effective biomarker for predicting not only pCR and survival outcomes but also chemotherapy-induced AEs for neoadjuvant platinum-based chemotherapy for breast cancer. It may help screen candidate responders and guide safety managements in the future.

Trial Registrion: SHPD001 (ClinicalTrials.gov identifier: NCT02199418) and SHPD002
(ClinicalTrials.gov identifier: NCT02221999).

Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Shanghai Natural Science Foundation [grant numbers 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant numbers 2018-15 and 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49 and ZH2018QNA42], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01 and PY2018-III-15], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty

Declaration of Interest: None to declare.

Ethical Approval: Ethical approvals were granted for both trials by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University.

Keywords: breast cancer, neoadjuvant chemotherapy, platinum, pathological complete response, Neo-Family History Score