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Long-Term Patterns of In-Breast Failure in Patients With Early Stage Breast Cancer Treated With Breast-Conserving Therapy

A Molecular Based Clonality Evaluation

McGrath, Samuel, MD*; Antonucci, John, MD*; Goldstein, Neal, MD; Wallace, Michelle, RN*; Mitchell, Chris, RN; Grills, Inga, MD*; Jolly, Shruti, MD§; Kestin, Larry, MD*; Vicini, Frank, MD*

American Journal of Clinical Oncology: February 2010 - Volume 33 - Issue 1 - p 17-22
doi: 10.1097/COC.0b013e31819cccc3
Original Articles: Breast

Background: The clonality of ipsilateral breast tumor recurrences (IBTR) after breast-conserving therapy (BCT) was established using a polymerase chain reaction-based allelic imbalance assay of microsatellite loci to compare tumor suppressor gene alteration patterns.

Methods: The clonality of IBTRs relative to the initial invasive carcinomas were analyzed using a polymerase chain reaction-based allelic imbalance assay in 57 patients treated with BCT, including both whole breast irradiation and accelerated partial breast irradiation.

Results: Thirty-four IBTRs (60%) were clonally related to the initial carcinoma and 23 (40%) were clonally different. Clonally related IBTRs were more frequently higher grade (70% vs. 32%, P = 0.019) and developed sooner after initial treatment (mean time interval to IBTR was 5.1 years in clonally related versus 9.3 years in clonally different cases [P = 0.002]). Twelve patients subsequently developed distant metastases, of which 9 (75%) had clonally related IBTRs. Clinical IBTR classification and molecular clonality assay results differed in 44% of all cases. The proportion of IBTRs that were clonally related at 5, 10, and 15 years after BCT were 82%, 48%, and 33%, respectively.

Conclusions: This analysis demonstrates the inaccuracy of clinically establishing the clonality of most IBTRs. Clonally related IBTRs occurred sooner than clonally different IBTRs, were more frequently associated with the development of distant metastases and had a worse prognosis. Molecular clonality assays provide a reliable means of identifying patients who may benefit from aggressive systemic therapy at the time of IBTR and provide an accurate assessment of the efficacy of various forms of local therapy.

From the *Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan; †Department of Pathology, William Beaumont Hospital, Royal Oak, Michigan; ‡Department of Radiation Oncology, William Beaumont Hospital, Troy, Michigan; and §Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.

Supported in part by a generous gift from the Alfred Berkowitz Foundation and the William Beaumont Hospital Foundation.

Presented at the 49th Annual Meeting of the American Society of Therapeutic Radiology and Oncology, Los Angeles, California, October 28th-November 1st, 2007.

Reprints: Frank A. Vicini, MD, Department of Radiation Oncology, Beaumont Cancer Institute, William Beaumont Hospital, 3601 W. 13 Mile Road, Royal Oak, MI. E-mail:

© 2010 Lippincott Williams & Wilkins, Inc.