Breast Cancer Subtype Approximated by ER, PR, and Her2 Receptors Is Associated With Local-Regional and Distant Failure After Breast-Conserving Therapy

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Appendix. Supplementary data
• Copyright

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Purpose/Objective(s) 

To determine whether breast cancer subtype, as approximated by estrogen receptor (ER), progesterone receptor (PR), and HER2/Neu (HER2) status, is associated with outcome after breast-conserving therapy (BCT).

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Materials/Methods 

The study cohort was comprised of 797 consecutive patients with invasive breast cancer who presented to the Dana-Farber Cancer Institute/Brigham and Women's Hospital (n = 451) or Massachusetts General Hospital (n = 346) from 7/1998 through 12/2001 for BCT and had ER, PR, and HER2 data. No patient received adjuvant trastuzumab. 88% of ER+orPR+ patients received hormonal therapy. Patients were assigned a breast subtype by receptor status: ERorPR+/HER2- = Luminal A, ERorPR+/HER2+ = Luminal B, ERandPR-/HER2+ = HER2+, ERandPR-/HER2- = Basal.

A competing risks method was used to analyze the time to isolated local or regional failure (LRF) as a first event, and the time to distant metastases (DM). The Gray's test was used to examine the association between breast subtype and cumulative incidence of LRF and DM after adjusting for known prognostic variables including age, dose, margins, lymphovascular invasion, grade, tumor size, node status, and use of systemic therapy.

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Results 

Median follow-up from diagnosis was 70 months. On univariable analysis (UVA) with Lum A as the baseline, the Lum B, HER2+, and Basal subtypes were associated with increased isolated LRF (Table). On multivariable analysis (MVA), the only significant associations with LRF were with the HER2+ and Basal groups.

On UVA with Lum A as the baseline, the Lum B, HER2+ and Basal groups were associated with an inreased risk of DM. On MVA, the factors associated with time to DM were number of positive nodes (AHR = 1.13, p < 0.001); tumor size (AHR = 1.30, p = 0.040); systemic therapy (AHR = 0.23, p = 0.005); grade 3 vs. grade 1 (AHR = 3.9, p = 0.042); and Lum B vs. Lum A (AHR = 2.72, p = 0.014). The association for Basal vs. Lum A was near-significant on MVA (AHR = 2.1, p = 0.073).

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Conclusions 

When approximated by ER, PR, and HER2 receptors, the HER2+ and Basal subtypes were independently associated with increased isolated local/regional failures after BCT compared to Lum A. Also, the Lum B, HER2+, and Basal subtypes were associated with an increased risk of distant metastases compared to Lum A, but after controlling for other known prognostic factors, the association was only significant for Lum B and near-significant for Basal. LRF in HER2+ patients treated with radiation and trastuzumab is not yet known. Prospective studies are needed to evaluate strategies to improve local control in these high-risk subtypes, especially in patients with Basal tumors.

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Appendix. Supplementary data 

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Appendix. Supplementary data 

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.ijrobp.2007.07.047