Subsets of Women With Close or Positive Margins After Breast-Conserving Surgery With High Local Recurrence Risk Despite Breast Plus Boost Radiotherapy

• Published in: International journal of radiation oncology, biology, physics Vol. 81; no. 4; pp. e561 - e568
• Main Authors: Lupe, Krystine, Truong, Pauline T., Alexander, Cheryl, Lesperance, Mary, Speers, Caroline, Tyldesley, Scott
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2011
• Subjects: Adult; Age Factors; Analysis of Variance; Breast cancer; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Breast Neoplasms - surgery; Breast-conserving therapy; British Columbia; Female; Follow-Up Studies; HAZARDS; Hematology, Oncology and Palliative Medicine; HISTOLOGY; Humans; Local recurrence; Lymphatic Metastasis; MAMMARY GLANDS; Mastectomy, Segmental; Middle Aged; Neoplasm Recurrence, Local - mortality; Neoplasm Staging; Neoplasm, Residual; NEOPLASMS; PATIENTS; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy boost; Radiotherapy Planning, Computer-Assisted; REGRESSION ANALYSIS; Retreatment; SIMULATION; SURGERY; Surgical margins; WOMEN; British Columbia; Surgical margins; Breast cancer; Breast-conserving therapy; Radiotherapy boost; Local recurrence
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2011.02.021

(1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. Subjects were 2,264 women with pT1–3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast ± boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer–specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age <45 years, 11.8% with Grade III, 11.3% with lymphovascular invasion (LVI), and 26.3% with ≥4 positive nodes. Corresponding rates in the negative margin cohort were 2.3%, 2.4%, 1.0%, and 2.4%, respectively. On Cox regression analysis of the entire cohort, close or positive margin, Grade III histology, ≥4 positive nodes, and lack of systemic therapy were significantly associated with higher LR risk. When close/positive margin cases were matched to negative margin controls, the difference in 5-year LR remained significant (4.25% vs. 0.7%, p < 0.001). On univariable analysis, subsets with close or positive margins, in combination with age <45 years, Grade III, LVI, and ≥4 positive nodes, have 5-year LR >10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery.