Research Unit in Medical Senology, Department of Medicine, European Institute of Oncology, Via Ripamonti 435, Milan, Italy.
Breast. 2009 Oct;18 Suppl 3:S137-40. doi: 10.1016/S0960-9776(09)70289-9.
Recommended principles for the choice of therapies in operable breast cancer include the recognition of diverse subtypes of breast cancer and, based on genetic signature and immunohistochemistry, the identification of targets and related factors predictive of response. We review recent developments in the knowledge of established predictive factors in the neo-adjuvant setting.
Experimental and clinical studies have shown that the degree of expression of estrogen receptor (ER) and progesterone receptor (PgR) of the primary tumor defines distinct biological entities that require a differentiated approach to neoadjuvant treatment and clinical trial investigation. In particular, tumors that express high levels of both steroid hormone receptors in a majority of cells derive no or low benefit from preoperative chemotherapy, while the absence of expression of ER and PgR was significantly correlated with the probability of pathologic complete remission (pCR). It was also demonstrated that the pCR rate to primary chemotherapy is significantly lower in invasive lobular carcinoma, frequently characterized by a high expression of steroid hormone receptors, if compared with the ductal histotype. Direct or indirect measures of high cell proliferation (elevated Ki-67 labeling index and high grade) identified patients with tumors responsive to chemotherapy in the preoperative setting. These factors might therefore assist in the identification of patients who might benefit from chemotherapy, in particular those patients with endocrine responsiveness. HER2 overexpression or amplification represents a target for neoadjuvant treatment with the humanised monoclonal antibody against its extracellular domain, but is also a factor predictive of response to neoadjuvant systemic therapies. A statistically significant positive correlation between HER2 positivity and pCR rate in patients treated with neoadjuvant chemotherapy was recently shown.
Results from studies in the neoadjuvant setting indicate that the use of factors predictive of response may permit a more effective application of therapies identifying patients likely to obtain substantial benefit from treatment.
可手术乳腺癌治疗选择的推荐原则包括识别不同的乳腺癌亚型，以及基于基因特征和免疫组织化学，确定预测反应的靶点和相关因素。我们综述了新辅助治疗中既定预测因素的最新研究进展。
实验和临床研究表明，原发肿瘤中雌激素受体（ER）和孕激素受体（PgR）的表达程度定义了不同的生物学实体，需要对新辅助治疗和临床试验研究采取差异化方法。特别是，大多数细胞中高表达这两种类固醇激素受体的肿瘤从术前化疗中获益甚微或几乎没有获益，而 ER 和 PgR 的表达缺失与病理完全缓解（pCR）的可能性呈显著相关。此外，与管状组织类型相比，浸润性小叶癌中对原发性化疗的 pCR 率显著较低，浸润性小叶癌通常具有高类固醇激素受体表达。细胞增殖的直接或间接标志物（高 Ki-67 标记指数和高分级）确定了在术前环境中对化疗有反应的患者。这些因素可能有助于识别可能受益于化疗的患者，特别是那些对内分泌治疗有反应的患者。HER2 过表达或扩增代表了用针对其细胞外结构域的人源化单克隆抗体进行新辅助治疗的靶点，但也是预测新辅助全身治疗反应的因素。最近的研究表明，HER2 阳性与接受新辅助化疗的患者 pCR 率之间存在统计学上的显著正相关。
新辅助治疗研究结果表明，使用预测反应的因素可以更有效地应用治疗方法，确定可能从治疗中获得实质性获益的患者。
