Does the volume of ductal carcinoma in situ impact the positive margin rate in patients undergoing breast conservation for invasive breast cancer?

BACKGROUND: We sought to investigate whether the volume of ductal carcinoma in situ (DCIS) impacts margin status in patients undergoing lumpectomy for invasive breast cancer. METHODS: We identified 358 patients with stages I-III invasive breast cancer and associated DCIS who were treated with breast-conserving therapy from 1999 to 2009. Data included patient and tumor characteristics, percentage of DCIS (<25%, 26%-50%, or >50%), and pathologic outcomes. Data were compared using chi-square and Fisher exact tests. A two-tailed P value of <0.05 was considered significant. RESULTS: The 358 patients had a mean age of 58 ± 13 y; 260 (72%) patients were >50 y. The volume of DCIS in lumpectomy specimens was <25% in 296 (83%) patients, 26%-50% in 29 (8%) patients, and >50% in 33 (9%) patients. Tumors with decreasing DCIS volume were more likely to be estrogen receptor positive (239 [82%] with <25% DCIS, 21 [72%] with 26%-50% DCIS, 22 [67%] with >50% DCIS; P=0.026). DCIS volume was not significantly associated with patient age, tumor size, grade, and stage, nodal status, progesterone receptor status, or Her2 status (P>0.05). Overall, 137 (38%) patients had one or more positive margins, including 97 of 296 (33%) with <25% DCIS volume, 17 of 29 (59%) with 26%-50% DCIS volume, and 23 of 33 (70%) with >50% DCIS volume (P<0.0001). CONCLUSIONS: The volume of DCIS associated with an invasive breast cancer in the final lumpectomy specimen is a strong predictor of positive surgical margins. Future analyses will focus on the ability of core pathology to provide this information for intraoperative surgical decision making.

Positive margin rates following breast-conserving surgery for stage I-III breast cancer: palpable versus nonpalpable tumors.

BACKGROUND: Margin status is a significant risk factor for local recurrence. We sought to examine whether the method of tumor localization predicted the margin status and the need for re-excision for both nonpalpable and palpable breast cancer. METHODS: We identified 358 consecutive breast cancer patients who were treated with breast-conserving therapy (BCT) from 1999 to 2006. Data included patient and tumor characteristics, method of localization (needle versus palpation), and pathologic outcomes. Descriptive statistics were used for data summary and data were compared using χ(2). RESULTS: Of 358 patients undergoing BCT, 234 (65%) underwent needle localization for a nonpalpable tumor and 124 (35%) underwent a palpation-guided procedure. Patients undergoing palpation-guided procedures were younger and had larger tumors at a more advanced pathologic stage of disease than those undergoing needle localization procedures (P < 0.05 for each). Patient race, tumor grade, presence of lymphovascular invasion, biomarker profile, and nodal status were not significantly different between the two groups (P > 0.05). Overall, 137 patients (38%) had one or more positive margins: 90 of 234 (38%) who had a needle localization procedure and 47 of 124 (38%) who had a palpation-guided procedure (P > 0.05). The number of margins affected did not differ significantly between the two groups. CONCLUSION: Although patients with palpable breast cancer had larger tumors than those with nonpalpable breast cancer, the incidence and number of positive margins was similar to those who had needle localization for nonpalpable tumors. Improved methods of localization are needed to reduce the rate of positive margins and the need for re-excision.

Compromised margins following mastectomy for stage I-III invasive breast cancer.

BACKGROUND: We investigated factors associated with positive margins following mastectomy and the impact on outcomes. METHODS: We identified 240 patients with stage I-III invasive breast cancer who underwent mastectomy from 1999 to 2009. Data included patient and tumor characteristics, pathologic margin assessment, and outcomes. Margin positivity was defined as the presence of in situ or invasive malignancy at any margin. Descriptive statistics were used for data summary and were compared using χ(2). RESULTS: Of the 240 patients, 132 (55%) had a simple mastectomy with sentinel lymph node biopsy and 108 (45%) had a modified radical mastectomy. Overall, 21 patients (9%) had positive margins, including 12 (57%) with one positive margin, 3 (14%) with two positive margins, and 6 (29%) with three or more positive margins. The most commonly affected margin was the deep margin (48% of patients). Eight of the 21 patients (38%) received adjuvant chest wall irradiation. There were no differences between patients who had a positive margin and those who did not with respect to patient age, race, percentage of in situ component, tumor size, tumor grade, lymphovascular invasion, or immunostain profile (P > 0.05 for all). None of the patients with positive margins experienced a local recurrence. CONCLUSIONS: Positive margins following mastectomy occurred in nearly 10% of our patients. No specific patient or tumor characteristics predicted a risk for having a positive margin. Despite the finding that only approximately 40% of patients received adjuvant radiation in the setting of a positive margin, no local recurrences have been observed.

Metastatic invasive breast cancer recurrence following curative-intent therapy for ductal carcinoma in situ.

BACKGROUND: The development of an invasive breast cancer recurrence outside of the breast parenchyma following curative-intent therapy for ductal carcinoma in situ (DCIS) is rare. We describe the patient and tumor characteristics associated with such recurrences. METHODS: A retrospective review was conducted of 621 patients who were treated for DCIS between 2004 and 2009. Patient, tumor, and treatment characteristics were collected. Descriptive statistics were utilized for data summary and data were compared using χ(2), where appropriate. RESULTS: Of 621 patients who underwent curative-intent therapy for DCIS, 12 (1.9%) developed an invasive metastatic recurrence. Primary local therapy at the time of the initial DCIS diagnosis included 11 patients who underwent mastectomy and one who had lumpectomy and adjuvant radiotherapy. The metastatic recurrences were in chest wall and/or ipsilateral axillary lymph nodes only (n = 6) or distant sites with or without ipsilateral axillary or supraclavicular lymph nodes (n = 6). Of the 12 patients with invasive recurrence, eight had high grade DCIS with comedo necrosis at initial diagnosis. The biomarker profiles of the invasive recurrences included 55% estrogen receptor positivity, 45% progesterone receptor positivity, and 73% Her2/neu amplification. Patient age, tumor grade, presence of comedo necrosis, biomarker profile, and surgical treatment were not predictive of recurrence. CONCLUSION: Invasive metastatic recurrence following adequate local therapy for DCIS is uncommon and likely represents progression of unidentified invasive disease at the time of diagnosis. The majority of invasive recurrences were Her2/neu amplified. Further studies are necessary to determine if such a unique biomarker profile correlates with metastatic recurrence.

Axillary staging prior to or after neoadjuvant systemic therapy? A single institutional experience.

BACKGROUND: The study aim was to investigate our institutional strategies for axillary staging in breast cancer patients undergoing neoadjuvant therapy. METHODS: We identified 595 patients treated with neoadjuvant therapy between 2000 and 2007. Axillary staging occurred by four methods: (1) pre-therapy fine needle aspiration biopsy (FNAB); (2) pre-therapy sentinel lymph node biopsy (SLNB); (3) post-therapy SLNB; or (4) post-therapy axillary lymph node dissection (ALND). RESULTS: Of 595 patients, 115 underwent FNAB (Group 1; 36 N0, 79 N+), 88 underwent SLNB pre-therapy (Group 2; 47 N0, 41 N+), 55 underwent SLNB post-therapy (Group 3; 42 N0, 13 N+), and 337 underwent ALND post-therapy (Group 4; 133 N0, 204 N+). There was no difference between groups according to patient age, race, stage of disease, estrogen/progesterone receptor and Her-2neu status, or type of neoadjuvant therapy. CONCLUSIONS: The lack of standardized recommendations for axillary staging in the setting of neoadjuvant therapy leads to variable approaches within an institution. The use of ALND without pre-therapy axillary assessment may result in over-treatment of patients. Randomized clinical trials are needed to determine the feasibility and accuracy of SLNB following neoadjuvant therapy. Until such data are available, pre-therapy axillary staging may reduce the number of unnecessary lymph node dissections.

Residual nodal disease in biopsy proven n1/n2 breast cancer following neoadjuvant systemic therapy.

BACKGROUND: The purpose of this study was to determine the rate of complete pathologic response in axillary lymph nodes after neoadjuvant therapy and the clinicopathologic factors associated with a complete response. METHODS: Clinical, demographic, and pathologic data from all patients with breast cancer treated at our institution are prospectively recorded in a database. We reviewed this database from 2000 to 2007 and identified 90 patients who were node-positive before neoadjuvant therapy based on image-guided fine needle aspiration biopsy; all 90 patients underwent axillary lymph node dissection (ALND) after neoadjuvant therapy. Data were compared using chi-square and Fisher's exact test. RESULTS: Of 90 patients with breast cancer who were node-positive before neoadjuvant therapy, 71 (79%) had positive nodal disease on final ALND pathology and 19 (21%) had a complete nodal pathologic response. Age, race, tumor grade, clinical T and N stage, and estrogen/progesterone receptor and Her-2neu status were not predictive of a complete nodal response. The only factor predictive of a complete nodal response was the type of neoadjuvant therapy used; all 19 patients with a complete response received neoadjuvant chemotherapy and none received neoadjuvant endocrine therapy (P < 0.05). CONCLUSIONS: Twenty-five percent of patients who underwent neoadjuvant chemotherapy had a complete pathologic response in the nodal basin, whereas no patient who underwent neoadjuvant endocrine therapy experienced a complete nodal response. Twenty-five percent of patients who underwent neoadjuvant chemotherapy had a complete pathological response in the nodal specimen, whereas no patient who underwent neoadjuvant endocrine therapy experienced a complete nodal response.

Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer.

BACKGROUND: The aim of the current study was to identify predictors of pathologic complete response (pCR) following neoadjuvant therapy. METHODS: From 2000 to 2007, 518 breast cancer patients received neoadjuvant therapy. Data were compared using chi(2) and Fisher's exact tests and multivariate analysis of variance, as appropriate. RESULTS: Of 518 breast cancer patients receiving neoadjuvant therapy, 81 (16%) had pCR (77 of 456 [17%] with chemotherapy, 4 of 62 [6%] with endocrine therapy; P < .05). Four factors were associated with pCR: higher tumor grade (P = .015), lack of estrogen receptor (ER) and progesterone receptor (PR) expression (P < .0001), HER2/neu amplification (P = .025), and negative lymph node status (P < .0001). On multivariate analysis, ER and PR negativity, HER2/neu amplification, and negative lymph node status were found to significantly correlate with pCR. CONCLUSIONS: Patients with ER-negative and PR-negative and HER2/neu-amplified breast cancer phenotypes are more likely to experience pCR to neoadjuvant therapy. Although pCR is more frequently observed following neoadjuvant chemotherapy, it is rare following neoadjuvant endocrine therapy.