Surgical Decision Making in the BRCA-Positive Population: Institutional Experience and Comparison with Recent Literature.

A retrospective study was performed to document the uptake and extent of surgical intervention in patients with a known mutation in the BRCA1/2 genes and associated outcomes. Data were collected retrospectively on BRCA-positive patients with and without cancer at the time of genetic testing. Our findings were compared to those published in the current literature. Of patients with cancer at testing, 61% chose bilateral mastectomies. Of patients without cancer, 54% chose risk-reducing surgery (RRS) including risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), or both. Time to surgery was significantly shorter to RRSO than to RRM. The literature suggests and our data support that acceptance of RRM in the BRCA-positive population has gradually increased over time. Consistently high rates of RRSO uptake and short intervals from time-of-testing to RRSO demonstrate that RRSO is still more acceptable to this population than RRM.

Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z1071 (Alliance).

OBJECTIVE: To evaluate factors affecting sentinel lymph node (SLN) identification after neoadjuvant chemotherapy (NAC) in patients with initial node-positive breast cancer. BACKGROUND: SLN surgery is increasingly used for nodal staging after NAC and optimal technique for SLN identification is important. METHODS: The American College of Surgeons Oncology Group Z1071 prospective trial enrolled clinical T0-4, N1-2, M0 breast cancer patients. After NAC, SLN surgery and axillary lymph node dissection (ALND) were planned. Multivariate logistic regression modeling assessing factors influencing SLN identification was performed. RESULTS: Of 756 patients enrolled, 34 women withdrew, 21 were ineligible, 12 underwent ALND only, and 689 had SLN surgery attempted. At least 1 SLN was identified in 639 patients (92.7%: 95% CI: 90.5%-94.6%). Among factors evaluated, mapping technique was the only factor found to impact SLN identification; with use of blue dye alone increasing the likelihood of failure to identify the SLN relative to using radiolabeled colloid +/- blue dye (P = 0.006; OR = 3.82; 95% CI: 1.47-9.92). The SLN identification rate was 78.6% with blue dye alone; 91.4% with radiolabeled colloid and 93.8% with dual mapping agents. Patient factors (age, body mass index), tumor factors (clinical T or N stage), pathologic nodal response to chemotherapy, site of tracer injection, and length of chemotherapy treatment did not significantly affect the SLN identification rate. CONCLUSIONS: The SLN identification rate after NAC was higher when mapping was performed using radiolabeled colloid alone or with blue dye compared with blue dye alone. Optimal tracer use is important to ensure successful identification of SLN(s) after NAC.

Margin re-excision and local recurrence in invasive breast cancer: A cost analysis using a decision tree model.

BACKGROUND: SSO-ASTRO recently published guidelines defining adequate margins in breast conservation therapy (BCT) as no tumor on ink based on studies demonstrating little difference in local recurrence (LR) with wider margins. We hypothesize that not routinely re-excising close margins results in decreased costs without compromising care. METHODS: A decision tree model was developed for the management of margins after BCT for invasive cancer. Patients were compared among three margin status groups: positive, close (≤2 mm) and negative (>2 mm). Ten publications provided re-excision rates (RER) and LR rates. The model assumed 140,000 BCT/year. Sensitivity analyses determined the most cost-effective strategy. Surgical costs were estimated using 2013 Medicare reimbursement rates. RESULTS: Re-excising close margins was significantly more costly than the alternative, $233.1 million versus $214.3 million, per year in the United States. Total surgical cost was most sensitive to re-excision of close margins-increasing the RER from 0% to 100% resulted in an $18.8 million cost difference. CONCLUSIONS: The strategy of re-excising close margins resulted in a predicted cost of $18.8 million per year. This does not include hospital costs, the cost of surgical complications after re-excision, and underestimates the potential savings by using Medicare reimbursement rates.

Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial.

OBJECTIVE: To determine the impact of tumor biology on rates of breast-conserving surgery and pathologic complete response (pCR) after neoadjuvant chemotherapy. BACKGROUND: The impact of tumor biology on the rate of breast-conserving surgery after neoadjuvant chemotherapy has not been well studied. METHODS: We used data from ACOSOG Z1071, a prospective, multicenter study assessing sentinel lymph node surgery after neoadjuvant chemotherapy in patients presenting with node-positive breast cancer from 2009 through 2011, to determine rates of breast-conserving surgery and pCR after chemotherapy by approximated biologic subtype. RESULTS: Of the 756 patients enrolled on Z1071, 694 had findings available from pathologic review of breast and axillary specimens from surgery after chemotherapy. Approximated subtype was triple-negative in 170 (24.5%), human epidermal growth factor receptor 2 (HER2)-positive in 207 (29.8%), and hormone-receptor-positive, HER2-negative in 317 (45.7%) patients. Patient age, clinical tumor and nodal stage at presentation did not differ across subtypes. Rates of breast-conserving surgery were significantly higher in patients with triple-negative (46.8%) and HER2-positive tumors (43.0%) than in those with hormone-receptor-positive, HER2-negative tumors (34.5%) (P = 0.019). Rates of pCR in both the breast and axilla were 38.2% in triple-negative, 45.4% in HER2-positive, and 11.4% in hormone-receptor-positive, HER2-negative disease (P < 0.0001). Rates of pCR in the breast only and the axilla only exhibited similar differences across tumor subtypes. CONCLUSIONS: Patients with triple-negative and HER2-positive breast cancers have the highest rates of breast-conserving surgery and pCR after neoadjuvant chemotherapy. Patients with these subtypes are most likely to be candidates for less invasive surgical approaches after chemotherapy.

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.

IMPORTANCE: Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies. OBJECTIVE: To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer. DESIGN, SETTING, AND PATIENTS: The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged. MAIN OUTCOMES AND MEASURES: The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease. RESULTS: Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%). CONCLUSIONS AND RELEVANCE: Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00881361.

Sentinel lymph node biopsy after neo-adjuvant chemotherapy in breast cancer.

The timing of sentinel node biopsy in the setting of neo-adjuvant chemotherapy for breast cancer is controversial. Sentinel node biopsy performed after neo-adjuvant chemotherapy may save patients with a nodal response the morbidity of an axillary lymph node dissection. A retrospective review of prospectively collected data compared sentinel node biopsies performed after patients had received neo-adjuvant chemotherapy with patients who had not received neo-adjuvant chemotherapy. Demographic factors, tumor characteristics, and the results of the sentinel node biopsies and completion lymph node dissections (when applicable) were compared. A total of 231 axillary procedures (224 patients) were evaluated. The patients who received neo-adjuvant chemotherapy (NEO; N=52) were younger, had higher grade tumors, were more likely to have a mastectomy, and were more likely to have ER-negative and HER-2/neu positive tumors than the patients who did not receive neo-adjuvant chemotherapy (NON; N=179). The mean clinical tumor size in the neo-adjuvant group was 4.5cm (±1.8) prior to chemotherapy; the post-chemotherapy pathologic size was 1.4cm (±1.3). A sentinel node was identified in all cases. There were no significant differences between the groups in the mean number of sentinel nodes removed (NEO=3.3; NON=3.1; p=0.545), the percentage of positive axillae (NEO=24%; NON=21%; p=0.776) or the mean number of positive sentinel nodes (NEO=1.3; NON=1.5; p=0.627). There was no difference in the percentage of completion lymph node dissections with additional positive nodes (NEO=20%; NON=35%; p=0.462); there was a difference in the number of nodes removed in the completion lymph node dissections (mean NEO=12.0; NON=16.4; p=0.047). Sentinel node biopsy performed after neo-adjuvant chemotherapy appears to be an oncologically sound procedure and may save some patients the morbidity of a complete lymph node dissection.

Effect of intraoperative radiocolloid injection on sentinel lymph node biopsy in patients with breast cancer.

BACKGROUND: Preoperative injection of radiocolloid before a sentinel lymph node (SLN) biopsy is painful for patients with breast cancer. Injection after anesthesia eliminates this discomfort but allows less time for radiocolloid migration. Our goal was to validate the efficacy of intraoperative injection. METHODS: In this retrospective study of prospectively collected data, patients underwent periareolar dermal injection of technetium sulfur colloid. Patients in the preoperative injection (PO) group were injected by radiologists in the breast imaging center. Patients in the intraoperative injection (IO) group were injected by surgeons after induction of anesthesia. Consecutive cases were evaluated for radioactive "hotspots," time elapsed before incision, number of SLNs removed, number of positive SLNs, and percentage of positive biopsies. RESULTS: Two hundred fourteen breasts were evaluated (PO = 102; IO = 112). The mean time from injection to incision was significantly shorter by 107 minutes for the IO group. There were no differences in the percentage of positive biopsies (PO: 20.6%; IO: 19.6%; P = 0.863), the number of SLNs removed (PO: 3.3; IO: 3.0; P = 0.091), or the number of positive SLNs (PO: 1.4; IO: 1.4; P = 0.657). CONCLUSIONS: There are no significant differences in the principal results of SLN biopsy between PO and IO injection methods. Dermal radiocolloid injection after induction of anesthesia seems to be an oncologically sound procedure and may be a preferable technique.

Rationale for Mastectomy after Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) reduces tumor size, facilitating the use of breast conservation surgery (BCS). However, mastectomy remains the surgical outcome for certain women. The goal of this study was to determine the rationale for mastectomy after NAC, particularly in women eligible for BCS. Retrospective data were reviewed on patients who received NAC between February 2006 and August 2010 at our institution. Demographics and tumor characteristics were compared between patients who received BCS and mastectomy after NAC. Of 149 patients meeting inclusion criteria, 102 (68%) underwent BCS and 47 (32%) underwent mastectomy. Patient preference was the most common rationale for mastectomy (n = 19; 40%), followed by extent of disease (n = 13; 28%), presence of a breast cancer susceptibility gene (BRCA) mutation (n = 9; 19%), persistent positive margins (n = 5; 11%), and wound complications (n = 1; 2%). Of the 47 patients who underwent mastectomy, 37 (79%) were eligible for BCS after NAC. Larger pathologic tumor size (2.05 vs 1.25 cm, P = 0.04) and lobular histology [invasive lobular carcinomas, n = 12/17 (70%) vs invasive ductal carcinomas, n = 36/133 (27%); P < 0.01] were associated with increased rate of mastectomy. After NAC, patient preference, extent of disease, and the presence of a BRCA mutation account for the vast majority of mastectomies. Interestingly, most of these patients were shown to be candidates for breast conservation. This highlights the importance of educating patients about their surgical choice and the lack of evidence, showing a benefit to more extensive surgery.

Application of ACOSOG Z1071: Effect of Results on Patient Care and Surgical Decision-Making.

BACKGROUND: The ACOSOG (American College of Surgeons Oncology Group) Z1071 assessed the feasibility of performing sentinel lymph node biopsy (SLNB) in node-positive patients who completed neoadjuvant chemotherapy (NACT). Historically, adoption of clinical research into practice takes years. The goal of this study was to determine the effect of Z1071 on our practice. MATERIALS AND METHODS: This is a retrospective review of Z1071's influence on a single institution's practice. Patients with biopsy-proven positive axillary lymph nodes before NACT were eligible for the study. After NACT, patients with nodal response according to imaging and exam were candidates for SLNB. Two cohorts were stratified according to diagnosis date before and after Z1071 results were presented on December 5, 2012 at the San Antonio Breast Cancer Symposium. Fisher exact tests and nonparametric rank tests were used to compare cohorts. RESULTS: The pre-Z1071 cohort included 74 patients and the post-Z1071 cohort 56 for a total of 130 patients. Post-Z1071, 73% (41/56) underwent a SLNB with an average of 4 nodes removed. Moreover, 27% (15/56) of patients had an axillary lymph node dissection as first intervention post-Z1071, compared with 99% (73/74) pre-Z1071. Axillary pathologic complete response pre-Z1071 was 35% (26/74) and post-Z1071 was 27% (15/56) (P = .35). CONCLUSION: This report shows that meaningful practice changes can be implemented rapidly. Changes in practice generated by clinical trial results should be monitored and outcomes followed.

Breast cancer detection in axillary sentinel lymph nodes: the impact of the method of pathologic examination.

At Carolinas Medical Center, before 2008, axillary sentinel lymph nodes (SLNs) from breast cancer patients were evaluated with a single hematoxylin and eosin-stained slide. In 2008, the protocol changed to include a limited step sectioning at 500 µm. In this study, we compared the intraoperative and permanent section pathologic findings for SLN biopsies from 2006 to 2007 to those from 2009 to 2010. We hypothesized that evaluating 2 slides would increase the detection of micrometastases and isolated tumor cells (ITCs) on permanent sections and correspondingly decrease the sensitivity of intraoperative touch preparation cytology (IOTPC). From 2006 to 2007, 140 (23.5%) of 597 of SLN permanent sections contained tumor cells: 92 macrometastases (65.7%), 36 micrometastases (25.7%), and 12 ITCs 0.2 mm or less (8.6%). The sensitivity of IOTPC for 2006 to 2007 was 51.4% for any tumor cells and 71.7% for macrometastases. From 2009 to 2010, 160 (21.9%) of 730 SLN permanent sections were positive for any tumor cells: 76 macrometastases (47.5%), 55 micrometastases (34.4%), and 29 ITCs (18.1%). The sensitivity of IOTPC for 2009 to 2010 was 39.4% for any tumor cells and 76.3% for macrometastases. With limited step sectioning, we observed an approximately 10% increase in the detection of both micrometastases and ITCs in SLN. The increased detection of ITCs on permanent sections reached statistical significance (P = .018). However, under current clinical guidelines, patients with limited SLN involvement may not be required to undergo completion axillary lymph node dissection. The ability to detect SLN tumor deposits less than 2 mm must be balanced with the clinical utility of doing so.