Intraoperative evaluation of surgical margins in breast cancer.

Achieving clear resection margins at the time of lumpectomy is essential for optimal patient outcomes. Margin status is traditionally determined by pathologic evaluation of the specimen and often is difficult or impossible for the surgeon to definitively know at the time of surgery, resulting in the need for re-operation to obtain clear surgical margins. Numerous techniques have been investigated to enhance the accuracy of intraoperative margin and are reviewed in this manuscript.

Association of body composition and surgical outcomes in patients with early-stage breast cancer.

BACKGROUND: Breast cancer is a disease that requires multimodality treatment, and surgical resection of the tumor is a critical component of curative intent treatment. Obesity, defined as a body mass index (BMI) > 30, has been associated with increased surgical complications. Additionally, sarcopenia, a condition of gradual loss of muscle mass, has been associated with worse breast cancer treatment outcomes. Sarcopenia occurs with increased age, inactivity, and poor diet leading to patient frailty, which can increase medical treatment complications. Even patients with high BMI can have sarcopenia (termed sarcopenic obesity). We investigated the association of sarcopenia with surgical complications for breast cancer. METHODS: A retrospective review was performed of patients diagnosed with breast cancer who received bioelectrical impedance spectrometry analysis of skeletal muscle mass and had surgery at our institution. Patient characteristics, treatment data, surgical type and complications were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status and BMI with surgical complications, adjusted for other patient characteristics. RESULTS: We analyzed 682 patients with stage I to III breast cancer. On multivariable logistic regression controlling for age, BMI, comorbidities, and types of surgeries (lumpectomy, mastectomy with or without reconstruction), sarcopenia (p = 0.66) was not associated with surgical complications. Obesity was associated with a higher rate of surgical complications in patients who received mastectomy with reconstruction (p = 0.01). More complex surgical approaches were associated with a higher risk of surgical complications in our series. CONCLUSION: Compared with those undergoing lumpectomy or mastectomy without reconstruction, patients undergoing mastectomy with reconstruction were more likely to experience postoperative complications and obesity was associated with higher risk of complication in the latter group. We did not identify a correlation between sarcopenia and rate of adverse surgical outcomes.

Association of sarcopenia with endocrine therapy toxicity in patients with early breast cancer.

BACKGROUND: Endocrine therapy reduces recurrence risk and improves survival in women with hormone receptor-positive breast cancer; however, side effects can decrease quality of life, leading to reduced treatment adherence. Sarcopenia is the loss of skeletal muscle mass that happens with age; it is associated with worse survival and reduced chemotherapy adherence in patients with breast cancer. The impact of sarcopenia on endocrine therapy tolerance has not been investigated. The current study evaluates the associations of sarcopenia with endocrine therapy toxicity and treatment tolerance. METHODS: Skeletal muscle mass was measured by bioelectrical impedance spectrometry. Skeletal muscle index (SMI) was calculated to assess for sarcopenia: SMI = (SMM kg)/(patient height, m2). Patients with SMI ≤ 6.75 kg/m2 were considered sarcopenic. A chart review was performed to obtain patient characteristics, endocrine therapy toxicity, and early treatment change or termination. Fisher's exact test was performed to associate patient characteristics and outcomes with sarcopenia status. RESULTS: Four hundred eighty-two patients with stage I-III breast cancer were prescribed endocrine therapy and had undergone sarcopenia evaluation. The median age was 61 years (29-88 years). Sarcopenia was identified in 35% of patients. Twelve percent of patients experienced grade 3-4 endocrine-related toxicities. On multivariable logistic analysis, sarcopenia was associated with increased odds of experiencing endocrine-related side effects (p = 0.006). In addition, patients with sarcopenia stopped or changed their medication due to side effects more often than those without sarcopenia (p = 0.03). CONCLUSION: The presence of sarcopenia in patients with EBC represents a potentially modifiable risk factor for more significant endocrine therapy side effects and reduced treatment tolerance.

Oncologic safety of axillary lymph node dissection with immediate lymphatic reconstruction.

PURPOSE: Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) can reduce the incidence of lymphedema in patients with breast cancer. The oncologic safety of ILR is unknown and has not been reported. The purpose of this study was to evaluate if ILR is associated with increased breast cancer recurrence rates. METHODS: Patients with breast cancer who underwent ALND with ILR from September 2016 to December 2020 were identified from a prospective institutional database. Patient demographics, tumor characteristics, and operative details were recorded. Follow-up included the development of local recurrence as well as distant metastasis. Oncologic outcomes were analyzed. RESULTS: A total of 137 patients underwent ALND with ILR. At cancer presentation, 122 patients (89%) had clinically node positive primary breast cancer, 10 patients (7.3%) had recurrent breast cancer involving the axillary lymph nodes, 3 patients (2.2%) had recurrent breast cancer involving both the breast and axillary nodes, and 2 patients (1.5%) presented with axillary disease/occult breast cancer. For surgical management, 103 patients (75.2%) underwent a mastectomy, 22 patients (16%) underwent lumpectomy and 12 patients (8.8%) had axillary surgery only. The ALND procedure, yielded a median of 15 lymph nodes pathologically identified (range 3-41). At a median follow-up of 32.9 months (range 6-63 months), 17 patients (12.4%) developed a local (n = 1) or distant recurrence (n = 16), however, no axillary recurrences were identified. CONCLUSION: Immediate lymphatic reconstruction in patients with breast cancer undergoing ALND is not associated with short term axillary recurrence and appears oncologically safe.

Stage IV Non-breast Cancer Patients and Screening Mammography: It is Time to Stop.

BACKGROUND: Patients diagnosed with metastatic cancer have shortened life expectancy with questionable benefit of routine screening mammography (SM). The aim of this study was to evaluate the incidence and consequences of continued SM in the setting of reduced survival from stage IV non-breast cancer. METHODS: Women diagnosed with Stage IV non-breast cancer at a single institution from 2015 to 2019 were queried from the institutional tumor registry for demographics, stage IV cancer diagnosis, and survival. Incidence and timing of SM after stage IV diagnosis and further diagnostic workup were extracted from the medical record. RESULTS: 790 women with Stage IV non-breast cancer were identified, 109 (14%) had at least 1 SM, 23% required diagnostic mammography, 7% breast biopsy, and 1% breast surgery. No breast cancers were identified. SM was ordered most often in stage IV gynecological cancers (28%), with more common cancers still seeing a high percentage of patients screened (lung 10%, colorectal 15%). Study 3-year survival was 26% (95% confidence interval [CI] 23-30%), with 74% mortality during follow up and median time from Stage IV diagnosis to death of 1.2 years (CI 0.4-2.3 years). Of patients screened, 41/109 died within 2 years of undergoing SM. CONCLUSIONS: Despite low overall survival for patients diagnosed with metastatic non-breast cancer, 14% of women underwent SM which resulted in additional imaging, biopsies, and surgery with no new breast cancers identified. Continued SM in this population offers risk without benefit of reduced breast cancer mortality and should no longer continue in women with stage IV non-breast cancer.

Invasive Lobular Breast Cancer: Data to Support Surgical Decision Making.

BACKGROUND: Invasive lobular carcinoma (ILC) is thought be a unique entity with higher rates of multifocal/multicentric and bilateral disease. This study aimed to evaluate the true extent of the disease, risk of bilaterality, lymph node involvement, and impact of preoperative imaging to help guide surgical decision making. METHODS: A retrospective analysis identified patients treated for ILC between 2004 and 2017. Clinical staging and pathologic results were compared. Follow-up details including local recurrence, contralateral breast cancer (CBC), and survival outcomes were evaluated. RESULTS: The study identified 692 patients with ILC, including 43 patients (6%) with a diagnosis of CBC and 232 patients (33%) with a diagnosis of multifocal/multicentric disease at presentation. Preoperative magnetic resonance imaging (MRI) led to an identification of additional disease in 20% of the patients. Preoperative MRI resulted in a more accurate prediction of tumor size staging but did not improve the discordance between clinical and pathologic nodal staging. Overall, the rate of imaging occult lymph node disease was 24%. At the 6-year follow-up evaluation, a local recurrence had developed in 2.3%, a CBC in 2.3, and a distant metastasis in 9.4% of the patients. The overall survival rate was 96% at 3 years and 91% at 5 years. CONCLUSIONS: Invasive lobular carcinoma is a distinct subset of cancer that poses a diagnostic staging challenge. The results of this study favor MRI for accurate tumor staging and for improving detection of multicentricity and bilaterality. However, clinicians should be aware of the higher likelihood of occult lymph node involvement with ILC and subsequent early metastasis.

Nipple-Sparing Mastectomy: Are We Providing Proper Prophylactic Antibiotic Coverage?

BACKGROUND: Infection after nipple-sparing mastectomy (NSM) and implant-based reconstruction (IBR) can be a devastating complication. The retained nipple may act as a portal or nidus for different ductal organisms, and as such, the bacteriology of surgical-site infections (SSIs) in this setting may not be adequately covered by current antibiotic recommendations. This study sought to evaluate SSI and reconstruction outcomes in relation to antibiotic choice and identify the different microbial species implicated. METHODS: A prospective database was reviewed for patients who underwent NSM with IBR from 2010 to 2019. Patient characteristics, operative details, antibiotic regimens, and subsequent treatment details were evaluated. The study analyzed SSI incidence, timing, and type of causative organisms. RESULTS: The study analyzed 571 NSMs with IBR performed for 347 patients (55% with direct implants and 45% with tissue expanders). The preoperative antibiotics consisted of cephalosporin alone for 65% of the patients, a more broad single-antibiotic use for 12% of the patients, and dual-coverage antibiotics for 20% of the patients. During a median follow-up of 1.7 years, SSI developed in 12% of the reconstructions, with 6% requiring prosthesis removal. The most common SSI organism cultured was Staphylococcal species. Neither pre- nor postoperative antibiotic choice was associated with incidence of infection, type of bacteria, or need for prosthetic explanation. CONCLUSION: For patients undergoing NSM with IBR, a more aggressive antibiotic choice is not associated with an improved SSI rate. Patient and treatment factors continue to carry the highest risk for SSI.

TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

BACKGROUND: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. METHODS: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). RESULTS: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. CONCLUSION: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

The Landmark Series: Adjuvant Radiation Therapy for Breast Cancer.

Radiation therapy represents a cornerstone of breast cancer treatment both for patients undergoing breast conservation and for those receiving mastectomy. Trials evaluating breast-conserving therapy have established the benefit of adjuvant radiation therapy in terms of both local control and breast cancer mortality, whereas trials evaluating post-mastectomy radiation therapy have demonstrated improved survival for appropriately selected patients. More recent trials have confirmed that axillary node dissection can be omitted for patients who have positive sentinel nodes with no impairment at locoregional recurrence and improved outcomes. Additionally, new studies have validated the finding that the addition of regional nodal irradiation to patients with limited nodal disease provides improved outcomes. With a growing focus on treatment de-intensification, studies evaluating partial-breast irradiation with brachytherapy and external beam have demonstrated outcomes comparable with those of whole-breast irradiation, whereas further study is needed regarding intraoperative radiation therapy. This study reviews these landmark studies to present a roadmap for how adjuvant radiation therapy is used to treat breast cancer patients at this time.

Lymphedema Prevention Surgery: Improved Operating Efficiency Over Time.

BACKGROUND: Lymphedema prevention surgery (LPS), which identifies, preserves, and restores lymphatic flow via lymphaticovenous bypasses (LVB), has demonstrated potential to decrease lymphedema in breast cancer patients requiring axillary lymph node dissection. Implementing this new operating technique requires additional operating room (OR) time and coordination. This study sought to evaluate the improvement of LPS technique and OR duration over time. METHODS: A prospective database of patients who underwent LPS at our institution from 2016 to 2019 was queried. Type of breast and reconstruction surgery, number of LVB performed, and OR times were collected. LPS details were compared by surgical group and year performed. RESULTS: Ninety-four patients underwent LPS, and 88 had complete OR time data available for analysis. Average age was 51 years, body mass index of 28, with an average of 15 lymph nodes removed. Reconstructive treatment groups included prosthetic reconstruction 56% (49), oncoplastic reduction 10% (9), and no reconstruction 34% (30). The number of patients undergoing LPS increased significantly from 2016 to 2019, and average number of LVB per patient doubled. In patients without reconstruction, the average time for LPS improved significantly from 212 to 87 min from 2016 to 2019 (p = 0.015) and similarly in patients undergoing LPS with prosthetic reconstruction from 238 to 160 min (p = 0.022). CONCLUSIONS: LVB is an emerging surgical lymphedema prevention technique. While requiring additional surgical time, our results show that with refinement of technique, over 4 years, we were able to perform double the number of LVB per patient in half the OR time.

Reducing Narcotic Prescriptions in Breast Surgery: A Prospective Analysis.

BACKGROUND: No clear standards regarding number or type of narcotics for adequate postoperative pain control have been established in breast surgery. The authors of this study reviewed their opioid-prescribing patterns and implemented a planned change, evaluated the effectiveness of a departmental practice adjustment, and prospectively evaluated patient narcotic usage. METHODS: The narcotic prescriptions for 100 consecutive breast surgery patients were reviewed to establish baseline postoperative narcotic-prescribing patterns. The median of narcotics prescribed was used to educate surgeons and implement a planned change in prescribing practices. Data on narcotic prescriptions for 100 consecutive breast surgery patients then were prospectively collected, and the number of pain pills the patients actually took after discharge was recorded using a standardized template. RESULTS: A baseline review of narcotic-prescribing practices showed that the median number of pills given was 15 for excisional biopsy/lumpectomy, 20 for mastectomy, and 28 for mastectomy with reconstruction. After departmental education, the median number decreased to 10 for excisional biopsy/lumpectomy (p < 0.01) and 25 for mastectomy with reconstruction (p < 0.01). Prospective recording of patient usage compared with the prescribed number of pills indicated that most prescribed pills were not used, with the excisional biopsy or lumpectomy patients using a median of 1 pill (p < 0.01), the mastectomy patients using a median of 3 pills (p < 0.01), and the mastectomy with reconstruction patients using a median of 18 pills (p < 0.01) postoperatively. Only three patients, all of whom had breast reconstruction performed, required a refill of narcotics. CONCLUSIONS: Successful reduction in narcotic prescriptions can be implemented for breast surgery patients. Further reductions in narcotic prescriptions may be feasible based on prospective collected patient usage.

Axillary reverse mapping and lymphaticovenous bypass: Lymphedema prevention through enhanced lymphatic visualization and restoration of flow.

BACKGROUND: A lymphedema (LE) prevention surgery (LPS) paradigm for patients undergoing axillary lymphadenectomy (ALND) was developed to protect against LE through enhanced lymphatic visualization during axillary reverse mapping (ARM) and refinement in decision making during lymphaticovenous bypass (LVB). METHODS: A retrospective analysis of a prospective database was performed evaluating patients with breast cancer who underwent ALND, ARM, and LVB from September 2016 to December 2018. Patient and tumor characteristics, oncologic and reconstructive operative details, complications and LE development were analyzed. RESULTS: LPS was completed in 58 patients with a mean age of 51.7 years. An average of 14 lymph nodes (LN) were removed during ALND. An average of 2.1 blue lymphatic channels were visualized with an average of 1.4 LVBs performed per patient. End to end anastomosis was performed in 37 patients and a multiple lymphatic intussusception technique in 21. Patency was confirmed 96.5% of patients. Adjuvant radiation was administered to 89% of patients. Two patients developed LE with a median follow-up of 11.8 months. CONCLUSION: We report on our experience using a unique LPS technique. Refinements in ARM and a systematic approach to LVB allows for maximal preservation of lymphatic continuity, identification of transected lymphatics, and reestablishment of upper extremity lymphatic drainage pathways.

Outcomes of Autologous Fat Grafting in Mastectomy Patients Following Breast Reconstruction.

BACKGROUND: Autologous fat grafting (AFG) is utilized for cosmetic improvement of the reconstructed breast following mastectomy. Fat necrosis (FN), a benign complication of AFG, can raise suspicion of malignancy and require further evaluation. OBJECTIVE: The aim of this study was to determine the incidence of FN in patients who have undergone AFG following mastectomy and reconstruction, and to identify factors contributing to FN. METHODS: A retrospective chart review was conducted of all patients who received AFG following mastectomy and reconstruction at our institution between 2011 and 2016, with a minimum 6-month follow-up period. Patient information, operative details, receipt of radiation, complications, and incidence of cancer recurrence were collected. RESULTS: A total of 171 patients were included in this study. AFG was performed by seven surgeons. Patients received an average of 1.18 treatments, with average follow-up of 26 months. Eighteen patients (10.5%) developed FN an average of 3.4 months following AFG. Patients with a larger volume injected at initial session (p = 0.044) and longer length of follow-up (p = 0.026) had significant increases in risk of developing FN. Core needle biopsy was performed in seven patients and two patients required excision. The rate of cancer recurrence was 1.7% for all patients and 0% in the AFG cohort. CONCLUSIONS: Increased risk of FN following AFG is associated with greater volume injected at the initial session and higher incidence over time. Although AFG is oncologically safe, patients should be counseled on the 10.5% incidence of FN presenting as a palpable abnormality, and the approximately 5% chance of requiring biopsy or excision.

Evaluation of recurrence patterns and survival in modern series of young women with breast cancer.

The data on oncologic outcomes in young women with breast cancer (BC) are dated as it relates to recurrences and mortality. Our goal was to assess these outcomes in a modern series of young women with BC. A retrospective chart review identified women ≤40 years old with stage I-III BC diagnosed from 2006 to 2013 at our institution. Demographics, tumor biology, type of operation, recurrence, and survival were analyzed. Overall, 322 women were identified. Most had ER+(70%) infiltrating ductal tumors (88%) with low stage (42% T1; 41% T2; 56% N0). Follow-up was 4.2 years with 5.6% local-regional recurrence (LRR), 15.2% metastatic recurrence (MR), and 8% mortality. There was no survival difference based on demographics, tumor biology, or type of operation. T3 tumors (P < .001) and node positivity (P < .001) were associated with worse disease-free survival. In this modern series of young women with BC, stage rather than tumor biology or surgical choice has more effect on recurrence-free survival. MR was more common than LRR, with most MR occurring within the first 2 years after surgery.

Determinants of short and long term outcomes in patients undergoing immediate breast reconstruction following neoadjuvant chemotherapy.

BACKGROUND: We evaluated oncologic outcomes and complications of skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate reconstruction (IR) after neoadjuvant chemotherapy (NAC) in patients with early-stage and locally advanced breast cancer (BC). METHODS: BC patients from 2000 to 2014 treated with NAC followed by SSM/NSM and IR were reviewed. Patient demographics, tumor characteristics, NAC response, complications, and recurrence were analyzed. RESULTS: Two hundred sixty-nine patients with 280 BCs were treated with NAC followed by SSM (94%) or NSM (6%) with IR. Median age was 47 (26-72) years with a median follow-up of 45 months. Pathologic complete response (pCR) was noted in 49 (17.5%) cases. Overall 30-day complication rate was 13.2%. Variables associated with complications included BMI (P < 0.0001), tobacco use (P = 0.015), and adjuvant radiation (P = 0.025). Local-regional recurrence was 3.2% and metastatic recurrence was 13.2%. Variables predicting recurrence risk were pre-NAC tumor size (P < 0.001), residual tumor size (P = 0.002), Grade III (P = 0.002), HER-2 negative (P = 0.025), pre-NAC nodal disease (P = 0.05), and lack of pCR (P = 0.045). CONCLUSION: Following NAC, risk factors for complications in patients undergoing SSM/NSM with IR are high BMI, smoking, and adjuvant XRT. SSM/NSM following NAC is associated with excellent local control. These data support expanding the indications for NSM/SSM to include patients receiving NAC.

Fertility in Women of Reproductive Age After Breast Cancer Treatment: Practice Patterns and Outcomes.

BACKGROUND: Breast cancer is the most frequently occurring cancer in women of reproductive age, and systemic treatments may adversely affect childbearing plans. Use of assisted reproductive technologies and therapies for ovarian protection improve fertility prospects. We evaluated whether patients had a documented fertility discussion (FD) with their oncology physician prior to therapy, what options were chosen, and if pregnancy was achieved. METHODS: A retrospective chart review from 2006 to 2014 was performed to evaluate women aged 40 years and younger who were diagnosed with breast cancer and treated with chemotherapy and/or antihormonal therapy. Patient demographics, treatment regimens, presence or absence of FD, in vitro fertilization (IVF) consultation, gonadotropin-releasing hormone (GnRH) agonist use, and subsequent successful pregnancy were analyzed. RESULTS: Among 303 patients meeting the inclusion criteria, 80 (26 %) had an FD with their physician documented; 71 of these 80 women (89 %) sought further fertility consultation and options. Sixteen (20 %) women were prescribed a GnRH agonist only for ovarian protection during chemotherapy, 50 (63 %) underwent IVF consultation only, and 5 (6 %) had both a GnRH agonist prescribed and an IVF consultation. The overall pregnancy rate was 7 % at a mean of 3 years post breast cancer treatment. Pregnancy after treatment was more common among those pursuing IVF consultation or prescribed a GnRH agonist. CONCLUSIONS: In treating young breast cancer patients, it is important to assess fertility desire, discuss treatment risks relating to fertility, and discuss preservation options. Although not every woman in this group desired pregnancy, 71/80 (89 %) women having a documented FD sought further fertility consultation and options.