Incidence and Consequence of Close Margins in Patients with Ductal Carcinoma-In Situ Treated with Mastectomy: Is Further Therapy Warranted?

Background

The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy.

Methods

The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years.

Results

Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1–2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p > 0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1–2.9 mm, and 0.7 % for margins ≥3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005).

Conclusions

Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.     

Treatment and outcome of patients with intracystic papillary carcinoma of the breast

BACKGROUND: Intracystic papillary carcinoma (IPC) of the breast is a rare form of noninvasive breast cancer. An appreciation of associated pathology with IPC may be critical in surgical decision-making. METHODS: The medical records of all patients with IPC treated between 1985 and 2001 were retrospectively reviewed. Three patient groups were identified according to the pathologic features of the primary tumor: IPC alone, IPC with associated ductal carcinoma in situ (DCIS), and IPC with associated invasion with or without DCIS. Types of treatment and outcomes were compared between groups. RESULTS: Forty patients were treated for IPC during the study period. Fourteen had pure IPC, 13 had IPC with DCIS, and 13 had IPC with invasion. The incidence of recurrence and the likelihood of dying of IPC did not differ between the three groups regardless of the type of surgery (mastectomy or segmental mastectomy) performed and whether radiation therapy was administered. The disease-specific survival rate was 100%. CONCLUSIONS: When IPC is identified, it is frequently associated with DCIS and or invasion. Standard therapy should be based on associated pathology. The role of radiation therapy in pure IPC remains to be determined.     

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.     

Improving local control with breast-conserving therapy: a 27-year single-institution experience

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.     

Physician recommendations regarding tamoxifen and patient utilization of tamoxifen after surgery for ductal carcinoma in situ

BACKGROUND: To date, the impact of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial reported in 1999 on the use of tamoxifen after surgery for ductal carcinoma in situ (DCIS) is unknown. The current study was designed to evaluate the impact of NSABP B-24 on current practices at a comprehensive cancer center. METHODS: The records of 350 consecutive patients with DCIS who were treated at the authors' institution between July 1999 and June 2002 were obtained from a prospective database and analyzed. Whether patients were offered tamoxifen, whether patients accepted tamoxifen, and the associated reasons were recorded along with tamoxifen-related side effects and patient compliance with therapy. Clinical and pathologic factors were evaluated for their impact on recommendations regarding tamoxifen. Differences were assessed by chi-square analysis. RESULTS: Of the 350 patients, 73 were excluded because of evidence of invasive carcinoma on final pathology review. Of the remaining 277 patients, 166 patients (60%) were offered tamoxifen, and 90 patients (54%) chose to take tamoxifen. Of 111 patients who were not offered tamoxifen, 39 patients (35%) had documented explanations, which included bilateral mastectomy (n = 25 patients), medical reasons (n = 10 patients), and already received tamoxifen for other reasons at the time of diagnosis (n = 4 patients). Of 94 patients who received tamoxifen, 20 patients (21%) discontinued use because of side effects or complications. Tamoxifen was more likely to be recommended for women who underwent segmental resection compared with women who underwent total mastectomy (P = 0.002) and for women with smaller pathologic DCIS tumors (P = 0.001). In addition, these two factors were interrelated. CONCLUSIONS: Physicians and patients remain cautious regarding the use of tamoxifen after local treatment for DCIS. The current findings have implications for current trials evaluating aromatase inhibitors and other chemopreventive agents for this disease.     

Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy

BACKGROUND: The current study identified determinants of systemic recurrence and disease-specific survival (DSS) in patients with early-stage breast carcinoma treated with breast-conserving surgery and radiation therapy (breast-conserving therapy, or BCT). METHODS: The study population consisted of 1,043 consecutive women with Stages I or II breast carcinoma who underwent BCT between 1970 and 1994. Clinical and pathologic characteristics evaluated included age, tumor size, tumor grade, estrogen and progesterone receptor status, surgical margins, axillary lymph node involvement, and use of adjuvant therapy. RESULTS: At a median follow-up time of 8.4 years, 127 patients (12%) had developed an ipsilateral breast tumor recurrence (IBTR), and 184 patients (18%) had developed a systemic recurrence. On multivariate logistic regression analysis, tumor size greater than 2 cm, positive lymph nodes, lack of adjuvant tamoxifen therapy, and positive margins (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.034) were predictors of systemic recurrence. When IBTR was added into the model, adjuvant therapy and surgical margins were not independent predictors; however, IBTR was an independent predictor of systemic recurrence (IBTR vs. no IBTR; OR, 6.2; 95% CI, 3.1-12.3; P < 0.001). The 10 year DSS rate after BCT was 87%. On multivariate Cox proportional hazards model analysis, the following factors were independent predictors of poor DSS: tumor size greater than 2 cm (vs. < or = 2 cm; relative risk [RR], 2.3; 95% CI, 1.2-4.3; P = 0.010), negative progesterone receptor status (vs. positive; RR, 2.7; 95% CI, 1.4-5.1; P = 0.003), positive margins (vs. negative; RR, 3.9; 95% CI, 1.4-11.5; P = 0.011), and IBTR (vs. no IBTR; RR, 5.5; 95% CI, 2.8-11.0; P < 0.001). CONCLUSIONS: Positive surgical margins and IBTR are predictors of systemic recurrence and disease-specific survival after BCT. Aggressive local therapy is necessary to ensure adequate surgical margins and to minimize IBTR.     

Factors impacting the accuracy of intra‐operative evaluation of sentinel lymph nodes in breast cancer

Sentinel lymph node dissection (SLND) is a standard axillary staging technique in breast cancer and intraoperative sentinel lymph node (SLN) assessment is important for decision‐making regarding additional treatment and reconstruction. This study was undertaken to investigate clinicopathologic factors impacting the accuracy of intraoperative SLN evaluation. Records of patients with clinically node‐negative, invasive breast cancer who underwent SLND with frozen section intraoperative pathologic evaluation from 2004 to 2007 were reviewed. Intraoperative SLN assessment results were compared to final pathology. Patients with positive SLNs that were initially reported as negative during intraoperative assessment were considered false negative (FN) events. Primary tumor histology, grade, receptor status, size, lymphovascular invasion (LVI), multifocality, neoadjuvant chemotherapy or hormonal therapy, number of SLNs retrieved, and SLN metastasis size were evaluated. The study included 681 patients, of whom 262 (38%) received neoadjuvant therapy. There were 183 (27%) patients who had a positive SLN on final pathology, of whom 60 (33%) had FN events. On univariate analysis, lobular histology, favorable histology, absence of LVI and micrometastasis were associated with a higher FN rate. On multivariate analysis, favorable and lobular histology and micrometastasis were independent predictors of FN events whereas LVI and receipt of neoadjuvant therapy were not statistically significant predictors. The accuracy of intraoperative SLN evaluation for breast cancer is affected by primary tumor histology and size of the SLN metastasis. There was no significant association between neoadjuvant therapy and the FN rate by intraoperative assessment. This information may be helpful in counseling patients about their risk for a FN intraoperative SLN assessment and for planning for immediate breast reconstruction in patients undergoing mastectomy.