Margaret M. Duggan

Impact of Margin Status on Local Recurrence After Mastectomy for Ductal Carcinoma In Situ

PURPOSE To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy. METHODS AND MATERIALS One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy. RESULTS The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence. CONCLUSIONS Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted.

Surgical Margins and the Risk of Local-Regional Recurrence After Mastectomy Without Radiation Therapy

PURPOSE Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. METHODS AND MATERIALS The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. RESULTS The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close (≤2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. CONCLUSIONS Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small.

Commonwealth of Massachusetts Board of Registration in Medicine Expert Panel on Immediate Implant-Based Breast Reconstruction Following Mastectomy for Cancer: Executive Summary, June 2011

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Abstract P6-12-05: The impact of residual disease after preoperative systemic therapy on clinical outcomes in patients with inflammatory breast cancer

Introduction. Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer treated with multimodality therapy consisting of preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM) and chest wall and regional nodal radiation and if appropriate extended biologic therapy and/or endocrine therapy. In non-IBC patients (pts) the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if the degree of pathologic response predicts clinical outcomes in IBC pts. Methods. With IRB approval, we reviewed the records of IBC pts seen at Dana Farber/Brigham and Womens Cancer Center between 1997 and 2012. From 117 IBC pts, all of whom have had PST, followed by MRM and radiotherapy, 98 pts with stage III disease were analyzed. Statistical analysis: TTR - time from surgery until first locoregional or distant recurrence, or censored at date of last follow-up or death of other causes. OS - time from surgery until death from any cause or censored at date the pt last known to be alive. Pathologic complete response (pCR) - no residual invasive disease in the breast and axillary lymph nodes. Pathologic response to PST, disease characteristics (estrogen (ER), progesterone receptor (PR), Her2 status, grade, histology) and receipt of Her2-directed PST when indicated were evaluated as predictors of TTR and OS by Cox model. Results 42 (43%) of 98 pts have experienced recurrence (1 local, 4 locoregional+distant, 31 distant). Median TTR = 5.1yrs. 40 pts died; 4 of other causes; median OS = 5.1yrs. pCR was associated with improved TTR (HR = 0.22, 95% CI 0.07-0.70, p = 0.011 univariate analysis); 5yr freedom from recurrence was 81% vs 40% with vs without pCR. The association remained after adjusting for disease and treatment characteristics (HR = 0.25, 95% CI 0.07-0.85, p = 0.026 multivariable). pCR was associated with better OS (HR = 0.35, 0.12-1.03, p = 0.06 multivariable). View this table: TTR and OS according to pCR or no pCR In multivariable modeling of TTR, lower tumor grade was associated with better outcome. Pts with ER, PR and Her2 negative or HER2+ disease without preoperative trastuzumab (H) had worse outcome (median TTR 0.9yr and 1.4yr); those with ER+ and/or PR+ HER2- disease and those with HER2+ disease who received preoperative H had 5yr freedom from recurrence 74% and 82%. View this table: TTR and OS according to ER, PR and Her2 status and receipt of neoadjuvant trastuzumab (H) Conclusions. Hormone receptor and HER2 status are independent prognostic features in IBC, similar to those seen in non-IBC. In addition, anti-Her2-directed preoperative therapy is important to improve outcomes of IBC pts with HER2+ disease. Understanding these features should help in the development of optimal therapies for IBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-05.

Surgical margins and the risk of local-regional recurrence (LRR) following mastectomy for early-stage breast cancer.

95 Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR. Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in...