Estrogen receptor, progesterone receptor, and HER2-neu expression in first primary breast cancers and risk of second primary contralateral breast cancer (original) (raw)

2012, Breast Cancer Research and Treatment

Background. The ACOSOG Z0011 trial demonstrated that axillary dissection (ALND) is not necessary for local control or survival in women with T1/2cN0 cancer undergoing breast-conserving therapy. There is concern about applying these results to triple-negative (TN) cancers secondary to their high local-recurrence (LR) rate. We examined the frequency of lymphovascular invasion (LVI) and nodal metastases in TN cancers to determine whether ALND can be safely avoided in this subtype. Methods. Data were obtained from a database of patients with invasive breast cancer treated at Memorial Sloan Kettering Cancer Center from January 1998 to December 2010. A total of 11,596 tumors were classifiable into clinical surrogates for molecular subtype by immunohistochemical analysis: hormone receptor (HR)?/HER2?, HR?/HER2-, HR-/HER2?, and TN (HR-/HER2-). Multivariable logistic regression analysis (MVA) was used to determine associations between clinicopathologic variables and subtype. Results. There were differences in age, tumor size, LVI, grade, and nodal involvement among groups. On MVA controlling for size, grade, and age, ER, PR, and HER2 status were significantly associated with LVI (p \ 0.0001). Relative to TN tumors, HR?/HER2-, HR?/HER2?, and HR-/ HER2? tumors had higher odds of demonstrating LVI of 1.8 (odds ratio 1.8; 95 % confidence interval 1.6-2.1), 2.5 (2.5; 2.0-3.0), and 1.7 (1.7; 1.4-2.1), respectively. On MVA adjusting for size, grade, LVI, and age, TN tumors had the lowest odds of having any or high-volume nodal involvement (C4 nodes, p \ 0.0001). Conclusions. LVI and nodal metastases were least frequent in TN cancers compared with other subtypes, despite the uniformly worse prognosis and increased LR rate in TN tumors. This suggests TN cancers spread via lymphatics less frequently than other subtypes and ALND may be avoided in TN patients meeting Z0011 eligibility criteria. Gene expression profiling has established that breast cancer comprises a group of biologically distinct diseases. 1,2 Expression levels of the estrogen receptor (ER) and progesterone receptor (PR), together defining hormone receptor (HR) status, and the HER2/neu receptor (HER2), characterize clinical surrogates for the molecular subtypes of breast cancer: HR?/HER2-(luminal Alike); HR?/ HER2? (luminal B-like); HR-/HER2? (HER2 tumors); and HR-/HER2-(triple-negative [TN], also referred to as basal-like). 3 Expression of these receptors can be measured by immunohistochemistry (IHC), allowing subtype classification to be widely applied in the clinical setting. This information is used to guide systemic therapy and to predict response to treatment and prognosis. 4-8 Patterns of recurrence and outcome differ among breast cancer molecular subtypes. 8-10 HER2 tumors, before the use of adjuvant trastuzumab, and TN tumors were associated with higher local recurrence (LR) rates and poorer overall survival (OS) than HR-positive tumors. 9,10 With the increased use of trastuzumab in the treatment of HER2overexpressing breast cancer (including the HR?/HER2? and HR-/HER2? subtypes), the rates of local failure and prognosis in this group have improved significantly, while TN breast cancers continue to have a poor prognosis and an increased rate of LR. 11 Given this, there is concern about adopting any treatment strategy with less aggressive local management for patients with TN breast cancers. In particular, there is concern about applying results of the American College of Surgeons Oncology Group (ACOSOG) Z0011