Older Patients With Certain Breast Cancer Subtype May Not Benefit From Radiation Therapy

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Newswise — CHICAGO — Local breast radiation therapy may not be necessary for women with the luminal A subtype of breast cancer, particularly those aged older than 60, according to study results presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

“Local breast radiation therapy, however, is still of benefit and is required for all the other breast cancer subtypes,” said Fei-Fei Liu, M.D., staff radiation oncologist at Princess Margaret Hospital, senior scientist at the Ontario Cancer Institute and professor at the University of Toronto, Ontario, Canada.

The researchers performed molecular subtyping for estrogen receptor (ER), progesterone receptor (PR), Ki-67, HER2, epidermal growth factor receptor and cytokeratin 5/6 on 304 tumor blocks from 769 women with breast cancer. These women had participated in a randomized trial in which they were assigned to tamoxifen and whole-breast radiation therapy or to tamoxifen alone. Based on the immunohistochemistry results, researchers classified patients into six categories: luminal A, luminal B, luminal-HER2, HER2-enriched, basal-like or triple-negative phenotype-nonbasal. They followed the patients for a median of 10 years.

Women in the luminal A subgroup, defined as ER-positive, PR-positive, HER2-negative and low Ki-67 (<14%), had the best outcome, with a 10-year risk for local relapse of 8 percent with tamoxifen alone vs. 4.6 percent with both tamoxifen and breast radiation therapy.

For luminal A patients aged older than 60, the local breast relapse rate was even lower at 4.3 percent with tamoxifen alone vs. 6 percent for tamoxifen plus breast radiation therapy, indicating that local breast radiation therapy did not contribute to the outcome of this group of patients, according to the researchers.

On the other hand, for other breast cancer subtypes, local breast radiation therapy was of definite benefit, according to Liu. For example, women with luminal B tumors had a recurrence rate of 16.1 percent with tamoxifen alone vs. 3.9 percent with tamoxifen and radiation therapy.

“If our data are validated with a larger number of patient tumor samples, we would recommend that Ki-67 be added to our current standard panel of ER, PR and HER2 testing for all patients with newly diagnosed breast cancer,” Liu said. “If the luminal A subtype is identified for lymph node-negative patients, especially for those 60 years old or older, then a discussion can be undertaken with these patients that if they take tamoxifen (or an equivalent medication) for their breast cancer, we might be able to avoid breast radiation therapy.

“This is yet another powerful example of ‘personalized cancer medicine.’ When this information is combined with well-conducted randomized clinical trials, significant advances can be made whereby we can truly start to tailor therapies, based on new molecular markers, which can be introduced into routine clinical practice.”

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Presenter: Fei-Fei Liu, M.D.

Abstract Number: 1032

Title: Post- menopausal women with luminal A subtype might not require breast radiotherapy: Preliminary results from a randomized clinical trial of tamoxifen + radiation

Author Block: Wei Shi1, Anthony Fyles1, Melania Pintilie1, Susan Done1, Naomi Miller1, Derek Wong1, Ivo A. Olivotto2, Lorna Weir2, David R. McCready1, Fei-Fei Liu1. 1Princess Margaret Hospital/University Health Network, Toronto, ON, Canada; 2Canada and the British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada

Objectives: To determine the predictive value for ipsilateral breast tumour recurrence (IBTR), molecular subtyping using six immunohistochemical (IHC) biomarkers were evaluated on the breast cancer specimens from patients age 50 and older with T1 and T2 node negative breast cancer, who were participants in a randomized trial of tamoxifen (Tam) +/- whole breast radiation (WBRT).Methods: Between December 1992 and June 2000, 769 women were randomized to WBRT and Tamoxifen (Tam/WBRT; n=386) 20 mg daily for 5 years, or Tam alone (Tam; n=383). Median age was 68 years; 639 (83%) had pT1 tumors. Intrinsic molecular subtyping was determined using semi-quantitative analysis of ER, PR, Ki-67, HER2, EGFR and cytokeratin (CK) 5/6 on tissue microarrays (TMAs) constructed from the tumor blocks of 304 of the 345 available tumors. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched, basal-like, or triple-negative phenotype-nonbasal. The median follow-up for this cohort was 10 years.Results: For the overall group, IBTR at 10 years was 13.8% with Tam compared to 5.0% with Tam/WBRT (p<0.0001). Tumour size (HR 1.54, p=0.001), ER positive status (HR 0.35, p=0.006), age (HR 0.96, p=0.014), and treatment with Tam/WBRT (HR 0.28, p<0.0001) were significant factors for IBTR. For the 304 TMAs, 145 patients were treated with Tam alone, 159 with both. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67<14%, n=133) had the lowest rate of IBTR: 8% with Tam alone vs. 4.6% with Tam/WBRT (p=0.3). In women aged > 60, IBTR was 4.3% with Tam alone vs. 6% with Tam/WBRT (n=103, p=0.9). Grade I/II Luminal A tumors (n=114) had a similar rate of IBRT regardless of treatment: 4.9% with Tam alone vs. 5.5% with Tam/WBRT (p=0.9). In contrast, luminal B tumours (Ki-67>14%, n=82) demonstrated an IBTR rate of 16.1% with Tam alone vs. 3.9% with Tam/WBRT (p=0.05). Lum HER2 (n=11), HER2-enriched (n=11) and basal-like (n=16) demonstrated even higher risks of IBTR, although the number is small in each group.Conclusions: These preliminary data demonstrate that the 6-marker IHC subtype appears to prognosticate for IBTR for women with early stage breast cancer. In particular, older (age >60) luminal A patients with grade I/II tumors demonstrated the lowest risk of breast relapse, for which RT had minimal impact, suggesting that such patients could be managed with Tam alone. It is of note that this subgroup represents a significant proportion of women in this trial (133/304 or 43%). In contrast, breast RT remains beneficial for women with higher risk subtypes (Luminal B, HER2 enriched, and basal). Further corroborations are required using the remaining tumour blocks, and validated in a prospective study.