【原】美国医学会杂志：乳腺癌治疗综述

　　大约12%的美国女性被诊断出乳腺癌，2017年美国新诊断乳腺癌病例超过25万。根据雌激素受体、孕激素受体、HER2分子标志的存在与否，乳腺癌被分为三种主要亚型：

• 激素受体阳性HER2阴性（约占70%）

• HER2阳性（约占15%～20%）

• 三阴性（约占15%）。

　　2019年1月22日，《美国医学会杂志》正刊发表哈佛大学医学院、达纳法伯癌症研究所的综述，总结了激素受体阳性HER2阴性、HER2阳性、三阴性乳腺癌的局部和全身循证治疗方法。

达纳法伯癌症研究所：哈佛大学医学院、哈佛大学公共卫生学院的教学医院之一，1947年由西德尼·法伯（现代化疗之父、儿童白血病医生）创建，1974年被命名为西德尼·法伯癌症研究所，1983年由查尔斯·安德森·达纳（美国记者、作家、官员，先后担任纽约论坛报和纽约太阳报总编、美国陆军助理部长）基金会提供支持，更名为达纳法伯癌症研究所。

　　超过90%的乳腺癌在诊断时尚未转移。对于尚未转移患者，治疗目标：通过局部治疗根治肿瘤、通过全身治疗预防复发。其中，三阴性乳腺癌与其他两种亚型相比，复发率较高，生存率较低，三阴性、HER2阳性、激素受体阳性Ⅰ期乳腺癌的5年乳腺癌相关生存率分别≥85%、≥94%、≥99%。

　　未转移乳腺癌的局部治疗包括：手术切除，单纯肿块切除术后考虑放疗。

　　未转移乳腺癌的全身治疗由亚型确定：

• 激素受体阳性乳腺癌患者接受内分泌治疗，少数接受化疗；

• HER2阳性乳腺癌患者接受HER2靶向抗体或小分子抑制剂治疗，联合化疗；

• 三阴性乳腺癌患者仅仅接受化疗。

　　全身治疗主要用于术后，即辅助治疗；某些全身治疗越来越多地被用于术前，即新辅助治疗。根据术前治疗效果调整术后治疗的研究正在进行。

　　对于已转移乳腺癌，根据亚型治疗，治疗目标：延长生命、缓解症状。　三阴性、HER2阳性、激素受体阳性已转移乳腺癌的中位总生存分别约为1年、5年、4～5年。

　　因此，乳腺癌由根据雌激素或孕激素受体表达和HER2基因扩增分类的三种主要肿瘤亚型组成，这三种亚型具有不同的风险特征和治疗策略。每位患者的最佳治疗取决于肿瘤亚型、癌症解剖分期、患者个人偏好。

JAMA. 2019 Jan 22;321(3):288-300.

Breast Cancer Treatment: A Review.

Adrienne G. Waks; Eric P. Winer.

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

This narrative review summarizes current evidence-based approaches to local and systemic treatment of hormone receptor positive/ERBB2 negative (HR+/ERBB2-), ERBB2 positive (ERBB2+), and triple-negative breast cancer.

IMPORTANCE: Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer.

OBSERVATIONS: Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2): hormone receptor positive/ERBB2 negative (70% of patients), ERBB2 positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer-specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive and ERBB2 positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor-positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients with ERBB2-positive tumors receive ERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performed. Increasingly, some systemic therapy is delivered before surgery. Tailoring postoperative treatment based on preoperative treatment response is under investigation. Metastatic breast cancer is treated according to subtype, with goals of prolonging life and palliating symptoms. Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for the other 2 subtypes.

CONCLUSIONS AND RELEVANCE: Breast cancer consists of 3 major tumor subtypes categorized according to estrogen or progesterone receptor expression and ERBB2 gene amplification. The 3 subtypes have distinct risk profiles and treatment strategies. Optimal therapy for each patient depends on tumor subtype, anatomic cancer stage, and patient preferences.

DOI: 10.1001/jama.2018.19323