The Genomic Landscape of Breast Cancer in Young and Older Women.

BACKGROUND: Young women with breast cancer (YWBC; ≤40 years) often have a poorer prognosis than older women with breast cancer (OWBC; ≥65 years). We explored molecular features of tumors from YWBC and OWBC to identify a biologic connection for these patterns. MATERIALS AND METHODS: We retrospectively analyzed the molecular profiles of 1879 breast tumors. Testing included immunohistochemistry (IHC), in situ hybridization (ISH), and next-generation sequencing. Statistical analyses included Pearson's chi2 test for comparisons, with significance defined as FDR (false discovery rate)-P < .05. RESULTS: TP53 and BRCA1 somatic mutations were more common in YWBC tumors than in OWBC tumors (53%, 42%; P = .0001, FDR-P = .0025 and 7%, 2%; P = .0001, FDR-P = .0025; respectively). Conversely, OWBC tumors had higher androgen receptor expression (55%, 45%; P = .0002, FDR-P = .0025) higher PD-L1 expression detected by IHC (8%, 5%; P = .0476, FDR-P = .2754), and more frequent PIK3CA mutations (33%, 17%; P = < .0001, FDR-P = < .0001). Among HR+/HER2- samples, YWBC had more gene amplifications in FGF3 (27%, 10%; P = .0353, FDR-P = .2462), FGF4 (27%, 9%; P = .0218, FDR-P = .1668), FGF19 (30%, 12%; P = .034, FDR-P = .2462) and CCND1 (37%, 18%; P = .0344, FDR-P = .2462) than OWBC. CONCLUSIONS: Our data suggest distinct molecular aberrations exist between YWBC and OWBC. Exploiting these molecular changes could refine our treatment strategies in YWBC and OWBC.

Assessment of Postmastectomy Radiation Therapy Receipt by Age and Association With Outcomes in Women With Breast Cancer.

PURPOSE: Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and improves overall survival (OS) in patients with breast cancer. Young age has been recognized as a risk factor for LRR. The primary objective of this study was to determine if recommendations for PMRT differed among patients younger than 50 years as compared to women aged 50 years or older. METHODS: We reviewed medical records of patients with breast cancer who underwent mastectomy with or without PMRT from 2010 through 2018. Univariable and multivariable models were used to estimate the association of age with PMRT. RESULTS: Of 2471 patients, 839 (34%) were <50 years; 1632 (66%) were ≥50 years. Patients <50 years had a higher percentage of grade 3 tumors, hormone receptor (HR) negative and/or Her-2/neu positive tumors, clinical stage T2/T3 tumors, and nodal involvement. Compared with patients ≥50 years, patients <50 years were more likely to undergo PMRT (OR 1.57; P = .001) and regional node irradiation (RNI) to the internal mammary nodes. Advanced clinical and pathologic stage, invasive tumor histology, the presence of lymphovascular invasion, and treatment with systemic chemotherapy were predictors of PMRT receipt for patients <50 years (P < .05). PMRT was associated with improved OS and recurrence free survival (RFS) among all patients (P < .01). CONCLUSION: Patients <50 years were more likely to undergo PMRT and to receive RNI to the internal mammary nodes but were also more likely to have other risk factors for recurrence that would warrant a PMRT recommendation. PMRT improved OS and RFS for all patients.

Young Age as a Predictor of Chemotherapy Recommendation and Treatment in Breast Cancer: A National Cancer Database Study.

INTRODUCTION: Breast cancer, although the second most common malignancy in women in the United States, is rare in patients under the age of 40 y. However, this young patient population has high recurrence and mortality rates, with chemotherapy frequently used as adjuvant treatment. We aimed to determine whether age is an independent predictor of chemotherapy recommendation and subsequent treatment and the relationship to Oncotype Dx (ODX) recurrence score (RS). METHODS: The National Cancer Database was retrospectively reviewed from 2010-2016 to identify women with early-stage (pT1-pT3, pN0-pN1mic, M0), hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer who underwent ODX RS testing. RESULTS: Of 95,382 patients who met the inclusion criteria, risk groups using the traditional ODX RS cutoffs were 59% low, 33% intermediate, and 8% high. Using Trial Assigning Individualized Options for Treatment RS cutoffs, risk groups were 23% low, 62% intermediate, and 15% high. Chemotherapy recommendation decreased as age at diagnosis increased (P < 0.001). Increasing age was associated with decreased odds of chemotherapy recommendation in univariate models both continuously (odds ratio: 0.98, 95% confidence interval 0.97-0.98; P < 0.001) and categorically by decade (P < 0.001). Age by decade remained an independent prognosticator of chemotherapy recommendation (P < 0.001), adjusted for risk groups. CONCLUSIONS: Chemotherapy recommendation and treatment differs by age among patients with early-stage hormone receptor positive breast cancer who undergo ODX testing. While molecular profiling has been shown to accurately predict the benefit of chemotherapy, younger age at diagnosis is a risk factor for discordant use of ODX RS for treatment strategies in breast cancer; with patients aged 18-39 disproportionately affected.

Anatomic Location of Tissue Expander Placement Is Not Associated With Delay in Adjuvant Therapy in Women With Breast Cancer.

BACKGROUND: Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown. METHODS: A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy. RESULTS: Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% ( P < 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction ( P < 0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival. CONCLUSIONS: Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment.

Effect of Delayed Oncoplastic Reduction Mammoplasty on Radiation Treatment Delay Following Breast-Conserving Surgery for Breast Cancer.

BACKGROUND: The purpose of this study was to evaluate the delay in initiating adjuvant radiation therapy (RT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer who underwent oncoplastic reduction mammoplasty (ORM) following BCS compared with a matched cohort of patients who did not undergo ORM between BCS and RT. METHODS: Medical records of 112 women (56 ORMs and 56 matched non-ORMs) with carcinoma in situ or early-stage breast cancer treated with BCS were reviewed. ORM was performed in a delayed manner following BCS, allowing confirmation of negative surgical margins. Time to RT was defined as time from last oncologic surgery to start of RT. RESULTS: The median follow-up time was 6.8 years for the ORM cohort and 6.7 years for the control non-ORM cohort. Patients who underwent ORM following BCS experienced a significant delay in initiating RT (>8 weeks) than matched patients not undergoing ORM (66% vs. 34%; p < 0.001). Wound complications occurred in 44.6% (n = 25) of patients in the ORM cohort, which were mostly minor, including delayed wound healing and/or infection (39%). There was no significant difference in local recurrence between patients in the non-ORM and ORM cohorts (p = 0.32). CONCLUSIONS: This study demonstrates that ORM following BCS has the potential to delay RT >8 weeks, largely as a result of increased risk of wound complications; however, this delay did not impact local control. ORM can be safely considered for appropriately selected patients with breast cancer.

Guidelines for breast cancer management in Bosnia and Herzegovina.

Breast cancer is the most common cancer among women. In Bosnia and Herzegovina, accurate data on the status of breast cancer are lacking due to the absence of a central registry. Multiple international guidelines imply that institutions that monitor breast cancer patients should have optimal therapeutic options for treatment. In addition, there have been several international consensus guidelines written on the management of breast cancer. Application of consensus guidelines has previously been demonstrated to have a positive influence on breast cancer care. The importance of specialty breast centers has previously been reported. As part of the 2021 Bosnian-Herzegovinian American Academy of Arts and Sciences (BHAAAS) conference in Mostar, a round table of multidisciplinary specialists from Bosnia and Herzegovina and the diaspora was held. All were either members of BHAAAS or regularly participate in collaborative projects. The focus of the consortium was to write the first multidisciplinary guidelines for the general management of breast cancer in Bosnia and Herzegovina. Guidelines were developed for each area of breast cancer treatment and management. These guidelines will serve as a resource for practitioners managing breast cancer in the Bosnia and Herzegovina region. This might also be of benefit to the ministry of health and any future investors interested in developing breast cancer care policies in this region of the world.

Integrative Oncology in Young Women With Breast Cancer.

Small studies have demonstrated the benefit of integrative oncology (IO) therapies in patients with breast cancer; however, referral patterns and timing of therapies are unknown. This study describes the referral pattern and utilization of IO services by young women with breast cancer. A retrospective review identified female patients, 40 years or younger, with a breast cancer diagnosis between 2014 and 2019, and a documented IO consultation. Patient demographics, cancer characteristics, treatments, reasons for seeking and timing of IO consultation, and IO treatment modalities were analyzed. The IO program treated 64 young women with a median age of 38.6 years. Clinical staging was primarily IA (27%), IIA (34%), or IIB (27%), and 64% of patients were clinically node negative with no evidence of metastasis. Women utilized the IO program for recurrence risk reduction and for treatment-related adverse effects (TRAEs), most commonly vasomotor complaints (44%). Therapies utilized were acupuncture (36%), healing touch (28%), oncology massage (30%), and other (75%; music therapy, therapeutic art, spiritual care, meditation, t'ai chi, yoga, and nutrition), which were commonly initiated during treatment (69%). Our data suggest that young women utilize IO services to reduce their future cancer risk and TRAEs, but they are often referred after standard cancer care treatments have begun. Future studies could examine the optimal timing for IO intervention.

Residual Cancer Burden Class Associated with Survival Outcomes in Women with Different Phenotypic Subtypes of Breast Cancer After Neoadjuvant Chemotherapy.

BACKGROUND: The residual cancer burden class informs survival outcomes after neoadjuvant chemotherapy. We evaluated the prognostic ability of the RCB for survival outcomes in women with different phenotypic subtypes of breast cancer treated with neoadjuvant chemotherapy. Additional variables were assessed for inclusion with the RCB to further improve the model's discriminative ability. PATIENTS AND METHODS: We conducted a retrospective review of patients completing at least 75% of the recommended cycles of neoadjuvant chemotherapy between 1 January 2010 and 31 December 2016. Phenotypic subtypes were defined by hormone receptor and human epidermal growth factor receptor 2 (HER2) status at diagnosis, classified as HR+/HER2-, HER2+, or triple-negative breast cancer (TNBC). The RCB class was calculated and survival endpoints of overall survival, recurrence-free survival, and distant recurrence-free survival were analyzed using Kaplan-Meier and Cox proportional hazards methods. The discriminative ability of the models was quantified by Harrell's C-index. RESULTS: Overall, 532 women met the inclusion criteria. Median follow-up was 65 months. In univariate models, RCB was significantly associated with OS, RFS, and DRFS. The RCB class had good discriminative ability for OS, RFS, and DRFS survival, with Harrell's C-indices of 0.68, 0.67, and 0.68, respectively. The RCB class discriminated well for each survival endpoint within HER2+ and TNBC, but did not discriminate well for HR+/HER2- (OS Harrell's C-indices of 0.77, 0.75, and 0.52, respectively). CONCLUSIONS: The RCB class was prognostic for OS, RFS, and DRFS after neoadjuvant chemotherapy, but prognostic discrimination between patients with subtype HR+/HER2- was not observed during the follow-up period for which the overall event rate was low.

Does Residual Cancer Burden Predict Local Recurrence After Neoadjuvant Chemotherapy?

BACKGROUND: The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR). METHODS: The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated. RESULTS: Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45; p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model. CONCLUSIONS: The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy.

Single surgeon versus co-surgeon bilateral mastectomy: Comparing outcomes and costs based on health economic modeling from the perspective of the hospital system.

INTRODUCTION: Co-surgeon approach for bilateral mastectomy may lead to shorter operative times and improved outcomes compared with single-surgeon approach, but cost differences remain unclear. Economic models were applied to determine whether either approach offered a lower cost opportunity. METHODS: A retrospective review of 409 patients undergoing single-surgeon or co-surgeon bilateral mastectomy between January 1, 2010 through April 30, 2016 was conducted. Outcomes included narcotic and antinausea doses, length of stay (LOS), and operative time. Analyses stratified by reconstruction and no reconstruction included Wilcoxon tests, Poisson regression, generalized linear models, and a cost calculator. RESULTS: Of 409 patients, 310 had reconstruction and 99 had no reconstruction. Compared with single-surgeon approach, co-surgeon approach was associated with less operative time and shorter LOS (233 vs. 250 min and 1.0 vs. 1.8 days no reconstruction; and 429 vs. 493 min and 2.2 vs. 2.8 days reconstruction). Economic analysis demonstrated less operative time, shorter LOS, and lower average cost for co-surgeon approach ($32,400 vs. $34,400 no reconstruction; and $76,700 vs. $79,400 reconstruction). CONCLUSION: Compared with the single-surgeon, the co-surgeon approach with reconstruction was associated with a statistically significant decrease in operative time and LOS. Economic analysis estimated the co-surgeon approach could lead to lower costs.

Ductal Carcinoma In Situ with Microinvasion on Core Biopsy: Evaluating Tumor Upstaging Rate, Lymph Node Metastasis Rate, and Associated Predictive Variables.

INTRODUCTION: The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. OBJECTIVE: Our aim was to assess the upstage rate to invasive cancer and axillary lymph node metastasis in patients diagnosed with DCISM, and whether predictive variables could be identified that may help inform who would most likely benefit from a surgical axillary evaluation. METHODS: We performed a retrospective review of 70 patients diagnosed with DCISM on core biopsy. Patients with concomitant or prior invasive cancer were excluded. Demographic, clinical, radiographic, histologic, and treatment data were collected. Fisher's exact test and univariable and multivariable logistic regression were performed to identify variables that may be associated with tumor upstaging and nodal metastasis. Time-to-event distributions were summarized using the Kaplan-Meier method. RESULTS: On final surgical pathology, 49 patients (70%) had a final diagnosis of DCISM or T1mi cancer, whereas 21 patients (30%) were upstaged to measurable invasive cancer (> 1 mm). One of 49 patients (2%) with DCISM on final pathology and 4 of 21 patients (19%) with measurable invasive cancer showed sentinel lymph node metastases. CONCLUSION: Although the upstage rate to measurable invasive cancer in our cohort of patients with DCISM on core biopsy was 30%, findings of a positive SLNB remain low at 7%. No predictive variables were identified to inform whether the routine practice of SLNB may be omitted in some patients with DCISM.

Rate of radial scars by core biopsy and upgrading to malignancy or high-risk lesions before and after introduction of digital breast tomosynthesis.

PURPOSE: Radial scars (RS) commonly present mammographically as architectural distortions, but these lesions may be associated with non-invasive and invasive breast cancer. Digital breast tomosynthesis (DBT) has resulted in higher detection rates of architectural distortion particularly in patients with dense breast tissue. We hypothesized that rates of clinically relevant lesions confirmed surgically would be lower in patients who received DBT imaging compared with those who received standard digital breast imaging. METHODS: We performed a retrospective review of 223 patients diagnosed with pure RS by core biopsy and surgical excision before and after DBT was introduced. The rate of upgrading to malignancy or high-risk lesion was evaluated. Demographics, biopsy type, and histologic data were analyzed. Univariable logistic regression analysis was used to identify variables that may be associated with upgrading. RESULTS: The rate of identifying RS increased from 0.04-.13% (P < 0.0001) with DBT imaging. The upgrade rate on surgical specimen to invasive or non-invasive cancer was similar before and after DBT; 6% versus 3%, as were findings of a high-risk lesion; 12% versus 22%. No predictive factors were identified for patients upgraded to malignant neoplasms or high-risk lesions. CONCLUSIONS: The likelihood of identifying RS has increased with DBT imaging, but rates of upgrading to a malignant neoplasm or high-risk lesion were similar to those before DBT. Although the rate of upgrading to malignancy after DBT was low, an excisional biopsy should be considered as 22% of patients were upgraded to high-risk lesions. These patients are candidates for chemoprevention and/or high-risk surveillance.

Changes in margin re-excision rates: Experience incorporating the "no ink on tumor" guideline into practice.

INTRODUCTION: Prior to the "no ink on tumor" SSO/ASTRO consensus guideline, approximately 20% of women with stage I/II breast cancers undergoing breast conservation surgery at our institution underwent margin re-excision. On May 20, 2013, our institution changed the definition of negative margins from 2 mm to "no ink on tumor." METHODS: A retrospective review was conducted of patients who had surgery at our institution with clinical stage I/II breast cancers between June 1, 2011 and May 1, 2015. In the pre-guideline cohort (pre) and post-guideline cohort (post), negative margins were 2 mm and "no ink on tumor," respectively. RESULTS: Implementation of the guideline resulted in a significant decrease in the positive/close margin rate (29.6% pre vs 10.1% post; P < 0.001) and numerical decrease in re-excision rate (20.4% pre vs 16.3% post; P = 0.104). No significant difference was found in local recurrence between the cohorts with limited follow-up (1.2% pre vs 1.5% post; P = 0.787). CONCLUSION: The implementation of the "no ink on tumor" guideline at our institution has resulted in a significant decrease in positive margin rates and a numerical decrease in margin re-excisions. In addition to margin status, surgeons continue to use individual patient and histologic factors to decide for or against margin re-excision.

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.

Simultaneous breast and axillary recurrence in a patient with a history of breast cancer and ipsilateral upper extremity melanoma: challenges in diagnosis and management.

BACKGROUND: Nodal patterns of spread for breast cancer and melanoma have been extensively studied in the literature. The phenomenon of upper extremity melanoma and ipsilateral breast cancer has been previously reported. We describe a rare case of a simultaneous locoregional recurrence of both malignancies. CASE REPORT: A patient with a previous diagnosis of stage 1A melanoma of the left upper extremity at age 29 developed left breast invasive ductal carcinoma 1 year later. The patient underwent a wide local excision with negative margins for the melanoma and a partial mastectomy with axillary dissection followed by chemotherapy and radiation therapy for her breast cancer. Five years later she was diagnosed with a dual recurrence while 36 weeks pregnant. CONCLUSIONS: Regular follow-up according to the NCCN guidelines is critical in diagnosing a recurrence of malignancy. Pathologic analysis is paramount in dictating management strategies in rare cases of dual recurrence.

Current prophylactic perioperative antibiotic guidelines in trauma: a review of the literature and outcome data.

A comprehensive review of prophylactic use of perioperative antibiotics in trauma from the 1970s to the present was performed. Evidence based guidelines were used to analyze the data from the past 32 years and define standards of care in the field. Recommendations and suggestions are provided to offer guidelines for prophylactic antibiotic use in trauma. Highlighted topics include general trauma surgery, with focus placed on abdominal and thoracic surgery in trauma, and non-trauma surgery, including subspecialties, for comparison.