Analysis of Risk of Recurrence by Subtype in ≤ 1-cm Breast Tumors

Abstract

Introduction

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with higher recurrence rates than other breast cancer subtypes. Increasing numbers of women are being diagnosed with early-stage breast cancer because of improvements in screening mammography. TNBC is known to be highly sensitive to chemotherapy; however, the benefit of adjuvant chemotherapy among women with ≤ 1-cm, lymph node-negative TNBC is unknown.

Materials and Methods

We evaluated the recurrence rates and recurrence-free survival of 437 women diagnosed with stage T1a-T1bN0 breast cancer from 1997 to 2009 at 2 institutions, with a median follow-up time of 6.2 years. Furthermore, we examined the treatment regimens of these women and evaluated the association of adjuvant chemotherapy with recurrence-free survival.

Results

Chemotherapy was administered more often to younger women and to women with high-grade, human epidermal growth factor receptor 2-positive or TNBC. Recurrence-free survival did not differ significantly between TNBC and estrogen receptor-positive breast cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.10-1.04; P = .058). After appropriate adjustments, no significant differences were detected in recurrence-free survival between the women who had received chemotherapy and those who had not among the women with TNBC (P = .132) or within any of the breast cancer subtypes (HR, 0.6; 95% CI, 0.2-1.9; P = .392).

Conclusion

Prospective trials of this subcentimeter node-negative breast cancer population are warranted to guide adjuvant chemotherapy decisions.

Introduction

The term “triple negative breast cancer” (TNBC) has been used to define the approximately 20% of breast cancer cases that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor 2 (HER2). TNBC has been recognized as an immunohistochemical surrogate for the basal-like subgroup of breast cancer as defined by gene expression analysis.¹ This subtype occurs more commonly among young women and women of African American descent and is biologically aggressive with a poor prognosis.² Similarly, HER2⁺ breast cancer is known to be more aggressive; however, relatively safe and effective targeted therapies, such as trastuzumab, are available.3, 4 Owing to the absence of well-defined molecular targets, cytotoxic chemotherapy has remained the mainstay of TNBC treatment. Cytotoxic chemotherapy is effective for TNBC, as evidenced by the high rates of pathologic complete response (pCR) after neoadjuvant chemotherapy, reported to be as high as 54.6%.5, 6 Previous studies have examined the benefit of adjuvant chemotherapy in patients with larger (> 1 cm) TNBCs, and it is clear that chemotherapy benefits such patients.⁷ However, the role of chemotherapy in smaller (≤ 1 cm) TNBC tumors is less clear.

With the increase in breast cancer awareness, more women obtaining annual mammograms, and the improvement in the sensitivity of digital mammography, early-stage breast cancers have been diagnosed with increasing frequency.⁸ Traditional risk stratification criteria, such as tumor size and lymph node status, are critically important; however, breast cancer subtypes, defined by ER, PR, and HER2 receptor status, represent additional prognostic information necessary to personalize the adjuvant treatment of early-stage breast cancer.9, 10, 11 Most clinical trials within breast cancer have included only women with tumors > 1 cm, aside from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-21, which did not have HER2 information available, and the recent adjuvant paclitaxel trastuzumab trial of node-negative HER2⁺ breast cancer, in which 46% of the tumors were ≤ 1 cm.12, 13 Thus, oncologists face decisions about adjuvant chemotherapy for women with small, node-negative TNBC with few prospective data for guidance.

Thus far, a series of small retrospective studies have examined the prognostic significance of receptor subtypes among stage T1a-T1bN0 breast tumors, with 5-year recurrence rates of TNBCs varying from 4% to 25%. Most of these studies have included small numbers of patients with TNBC, and all were limited because of the large numbers of women who had received adjuvant chemotherapy, making it difficult to attribute the measured recurrence rates to the natural history of small node-negative breast tumors or the administration of chemotherapy.14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28

The present dual-institution, retrospective cohort study aimed to understand the recurrence-free survival of patients with small (≤ 1 cm), lymph node-negative tumors that are TN compared with small tumors of other biologic subtypes. We have described the treatment patterns among these differing subgroups of women with breast cancer and explore the utility of adjuvant cytotoxic chemotherapy in this population.