Investigating the Link between Lynch Syndrome and Breast Cancer.

OBJECTIVE: Lynch syndrome is an inherited genetic disorder associated with a predisposition to early-onset colorectal and endometrial cancers, but breast cancer risk in these patients is debated. The aim of this study is to evaluate breast cancer rates in a cohort of Lynch syndrome patients, as well as to identify women who may be eligible for additional breast cancer specific genetic testing or enhanced breast surveillance (contrast-enhanced magnetic resonance imaging (MRI) screening). MATERIALS AND METHODS: Using a hereditary colorectal cancer registry at a single academic institution for identification of patients with Lynch syndrome, a retrospective chart review was performed of 188 women with DNA mismatch repair (MMR) mutations. The Tyrer-Cuzick model was used to estimate breast cancer risk in patients without breast cancer. RESULTS: The prevalence of breast cancer differed based on mutation type (p=0.0043), as 27% of women with a PMS2 mutation were diagnosed with breast cancer, compared to 3%, 4%, and 9% in MLH1, MSH2, and MSH6 patients. The average age at diagnosis for women with a PMS2 mutation was 46.7 years. Additionally, 7.5% of unaffected women had an estimated lifetime risk of breast cancer greater than 20%. 46/188 (24.4%) of patients were eligible for breast specific genetic testing. CONCLUSION: Our analysis suggests that Lynch syndrome patients with PMS2 mutations may be at higher risk of developing breast cancer. Additionally, the personal and family history of cancer suggests crossover in eligibility for breast specific genetic testing in a significant number of patients (16.5-24.4%). Also, many women are eligible for enhanced breast surveillance (7.5%) which would otherwise not be offered.

Near Infrared Fluorescent Lymph Node Mapping with Indocyanine Green in Breast Cancer Patients: A Prospective Trial.

BACKGROUND: Near infrared (NIR) fluorescence imaging is an emerging modality that can enable real-time image-guided procedures. Indocyanine green (ICG) is an FDA-approved, inexpensive, and widely available NIR dye. We hypothesized that axillary lymphatic mapping with ICG is equivalent to lymphatic mapping with technetium 99m (99mTc) in breast cancer patients. STUDY DESIGN: Breast cancer patients (cT1-2, N0) were prospectively enrolled. Patients underwent lymphatic mapping with 99mTc preoperatively and ICG mapping intraoperatively (0.8 mL). Sentinel lymph node (SLN) biopsy was guided by NIR camera and gamma probe. Rate of failed mapping, number of SLNs identified, and rate of identifying pathologically positive SLNs were compared between the 2 techniques (p < 0.05 was considered statistically significant). RESULTS: Ninety-two female patients were enrolled (median age 59 years). Mean transit time from ICG injection in the breast to localization in the axilla was 5 minutes (range 2 to 29 minutes). No adverse reactions to ICG were noted. Mean number of SLNs identified with ICG and 99mTc was 2.4 (SD 1.42) and 2.2 (SD 1.23), respectively (p = 0.34). Pathologically positive SLNs were identified in 18 (19.8%) patients. A total of 24 pathologically positive SLNs in 18 patients were identified by ICG in 24 of 24 (100%) patients and by 99mTc in 23 of 24 (96%) patients (p = 0.99). CONCLUSIONS: Indocyanine green with NIR fluorescence imaging can be safely and efficiently used for real-time intraoperative lymphatic mapping in breast cancer patients. Indocyanine green performs similarly to 99mTc with regard to the number of SLNs identified, rate of failed mapping, and identification of pathologically positive SLNs.

Oncotype testing in patients undergoing intraoperative radiation for breast cancer.

Oncotype DX recurrence score (RS) predicts risk of distant disease recurrence, and can guide chemotherapy recommendations in hormone positive, human epidermal growth factor 2-negative, early stage breast cancer. The present study aimed to evaluate the pattern of oncotype testing, RS and adjuvant treatment in patients undergoing intraoperative radiotherapy (IORT). Single center prospective data registry was queried for patients receiving IORT between October 2011 and February 2017. Patient demographics, tumor characteristics, RS, systemic therapy and recurrence information were analyzed. A total of 150 women with mean age of 70.8 years were included. The majority had invasive ductal cancer (60.6%) with 1.0 cm average tumor size and no lymph node involvement (99%). Oncotype testing was performed in 36 patients (24.3%). Low risk score (<18) was confirmed in 19 women (53%); intermediate risk score (18-30) in 16 women (44%); and high risk score (>30) in one woman (3%). Patients with RS testing had significantly increased tumor sizes (1.2 vs. 1.0 cm; P<0.001) and were younger (68.5 vs. 71.3 years; P=0.02) compared with those not tested. A total of 4/150 patients (2.6%) received chemotherapy; two received chemotherapy based on RS testing. Based on the current selection criteria for IORT, oncotype testing rarely results in a high-risk score or utilization of chemotherapy for IORT patients. The present study supports selective use of RS testing in IORT patients and confirms that biologically low-risk patients are being selected for IORT based on current guidelines.

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.

Impact of Multigene Panel Testing on Surgical Decision Making in Breast Cancer Patients.

BACKGROUND: With the advent of multigene panel testing for breast cancer patients, germline mutations with unknown association with cancer risk, known as variants of uncertain significance (VUS), are being increasingly identified. Some studies have shown higher rates of contralateral prophylactic mastectomies (CPM) in these patients, despite lack of evidence to support this intervention. We analyzed surgical choices in patients who were identified to have VUS. STUDY DESIGN: A retrospective review was performed of patients with triple-negative breast cancer treated at a single institution after multigene panel tests became available (September 1, 2013 to February 28, 2017). Rates of genetic testing, results of testing, and surgical decision making were evaluated. Chi-square or Fisher's exact test was used to compare categorical variables. A p value <0.05 was considered statistically significant. RESULTS: There were 477 triple-negative breast cancer patients identified; 331 met established criteria for genetic testing and 226 (68.3%) underwent genetic testing (multigene panel, n = 130 and BRCA1/2 testing, n = 96). All of them received risk-appropriate genetic counseling and follow-up. Of these, 29 (12.8%) patients had pathogenic mutations in BRCA1/2 or PALB2 (Mut+), 42 (18.6%) had VUS (VUS+), and 155 (68.6%) had no mutations identified (Mut-). Variants of uncertain significance in 6 of 42 patients (14.3%) were later reclassified as normal variants. Eighty-eight percent of Mut+ patients underwent CPM compared with 20.1% of Mut- and 21.4% of VUS+ patients (p < 0.001 for both). Rates of CPM were not significantly different between VUS+ and Mut- (p = 0.37). Multigene panel testing detected pathogenic mutations in non-breast cancer-associated genes in 6 patients, with significant management implications. CONCLUSIONS: When combined with risk-appropriate genetic counseling, detection of VUS did not lead to excessive CPM in this cohort of triple-negative breast cancer patients. Furthermore, panel testing detected mutations in non-breast cancer-associated genes, which had significant implications on management and outcomes.

Impact of an embedded genetic counselor on breast cancer treatment.

BACKGROUND: We predicted that embedding a genetic counselor within our breast practice would improve identification of high-risk individuals, timeliness of care, and appropriateness of surgical decision making. The aim of this study is to compare cancer care between 2012 and 2014, prior to embedding a genetic counselor in the breast center and following the intervention, respectively. METHODS: A retrospective review of patients diagnosed with breast cancer in 2012 (n = 471) and 2014 (n = 440) was performed to assess patterns of medical genetics referral, compliance with referral, genetic testing findings, and impact on treatment. RESULTS: Between 2012 and 2014, patients were 49% more likely to be referred to genetics, 66% more likely to follow through with their genetic counseling appointment, experienced a 73% reduction in wait times to genetic counseling visits and 69% more likely to have genetic testing results prior to surgery. Notably, while the number of genetic mutations identified was in the expected range over both time periods (9% of those tested in 2012 vs. 6.6% of those tested in 2014), there was a 31% reduction in time to treatment in 2014 vs. 2012. CONCLUSION: Awareness of germline genetic mutations is critical in surgical decision making for newly diagnosed breast cancer patients. Having an experienced genetics specialist on site in a busy surgical breast clinic allows for timely access to genetic counseling and testing, and may have influenced time to treatment in our institution.

Intraoperative Radiation for Breast Cancer with Intrabeam™: Factors Associated with Decreased Operative Times in Patients Having IORT for Breast Cancer.

INTRODUCTION: Intraoperative radiation with Intrabeam™ (IORT) for breast cancer is a newer technology recently implemented into the operating room (OR). This procedure requires time and coordination between the surgeon and radiation oncologist, who both perform their treatments in a single operative setting. We evaluated the surgeons at our center, who perform IORT and their OR times to examine changes in OR times following implementation of this new surgical procedure. We hypothesized that IORT is a technique for which timing could be improved with the increasing number of cases performed. METHODS: A prospectively maintained IRB approved database was queried for OR times (incision and close) in patients who underwent breast conserving surgery (BCS), sentinel lymph node biopsy with and without IORT using the Intrabeam™ system at our institution from 2011 to 2015. The total OR times were compared for each surgeon individually and over time. Next, the OR times of each surgeon were compared to each other. Continuous variables were summarized and then a prediction model was created using IORT time, OR time, surgeon, and number of cases performed. RESULTS: There were five surgeons performing IORT at our institution during this time period with a total of 96 cases performed. There was a significant difference observed in baseline surgeon-specific OR time for BSC (p = 0.03) as well as for BCS with IORT (p < 0.05), attributable to surgeon experience. The average BCS times were faster than the BCS plus IORT procedure times for all surgeons. The overall mean OR time for the entire combined surgical and radiation procedure was 135.5 min. The most common applicator sizes used were the 3.5 and 4 cm, yielding an average 21 min IORT time. Applicator choice did not differ over time (p = 0.189). After adjusting for IORT time and surgeon, the prediction model estimated that surgeons decreased the total BCS plus IORT OR time at a rate of -4.5 min per each additional 10 cases performed. CONCLUSION: Surgeon experience and applicator size are related to OR times for performing IORT for breast cancer. OR time for IORT in breast cancer treatment can be improved over time, even among experienced surgeons.

Are Patients Traveling for Intraoperative Radiation Therapy?

PURPOSE: One benefit of intraoperative radiation therapy (IORT) is that it usually requires a single treatment, thus potentially eliminating distance as a barrier to receipt of whole breast irradiation. The aim of this study was to evaluate the distance traveled by IORT patients at our institution. METHODS: Our institutional prospective registry was used to identify IORT patients from 10/2011 to 2/2017. Patient's home zip code was compared to institution zip code to determine travel distance. Characteristics of local (<50 miles), regional (50-100 miles), and faraway (>100 miles) patients were compared. RESULTS: 150 were patients included with a median travel distance of 27 miles and mean travel distance of 121 miles. Most were local (68.7%), with the second largest group living faraway (20.0%). Subset analysis of local patients demonstrated 20.4% traveled <10 miles, 34.0% traveled 10-20 miles, and 45.6% traveled 20-50 miles. Six patients traveled >1000 miles. The local, regional, and faraway patients did not differ with respect to age, race, tumor characteristics, or whole breast irradiation. CONCLUSIONS: Breast cancer patients are traveling for IORT, with 63% traveling >20 miles for care. IORT is an excellent strategy to promote breast conservation in selected patients, particularly those who live remote from a radiation facility.