TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have overall poor clinical outcomes, with triple-negative IBC (TN-IBC) being associated with the worst survival, warranting the investigation of novel therapies. Preclinical studies implied that ruxolitinib (RUX), a JAK1/2 inhibitor, may be an effective therapy for TN-IBC. METHODS: We conducted a randomized phase II study with nested window-of-opportunity in TN-IBC. Treatment-naïve patients received a 7-day run-in of RUX alone or RUX plus paclitaxel (PAC). After the run-in, those who received RUX alone proceeded to neoadjuvant therapy with either RUX + PAC or PAC alone for 12 weeks; those who had received RUX + PAC continued treatment for 12 weeks. All patients subsequently received 4 cycles of doxorubicin plus cyclophosphamide prior to surgery. Research tumor biopsies were performed at baseline (pre-run-in) and after run-in therapy. Tumors were evaluated for phosphorylated STAT3 (pSTAT3) by immunostaining, and a subset was also analyzed by RNA-seq. The primary endpoint was the percent of pSTAT3-positive pre-run-in tumors that became pSTAT3-negative. Secondary endpoints included pathologic complete response (pCR). RESULTS: Overall, 23 patients were enrolled, of whom 21 completed preoperative therapy. Two patients achieved pCR (8.7%). pSTAT3 and IL-6/JAK/STAT3 signaling decreased in post-run-in biopsies of RUX-treated samples, while sustained treatment with RUX + PAC upregulated IL-6/JAK/STAT3 signaling compared to RUX alone. Both treatments decreased GZMB+ T cells implying immune suppression. RUX alone effectively inhibited JAK/STAT3 signaling but its combination with PAC led to incomplete inhibition. The immune suppressive effects of RUX alone and in combination may negate its growth inhibitory effects on cancer cells. CONCLUSION: In summary, the use of RUX in TN-IBC was associated with a decrease in pSTAT3 levels despite lack of clinical benefit. Cancer cell-specific-targeting of JAK2/STAT3 or combinations with immunotherapy may be required for further evaluation of JAK2/STAT3 signaling as a cancer therapeutic target. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , NCT02876302. Registered 23 August 2016.

Second primary non-breast cancers in young breast cancer survivors.

PURPOSE: We evaluated the incidence, timing, and risk factors for second primary non-breast cancers (SPNBC) among young breast cancer (BC) survivors. METHODS: This study included participants of the Young Women's BC Study (YWS) who were diagnosed with stage 0-III BC between 2006 and 2016 and age 40 or younger at diagnosis (N = 1,230). Patient characteristics, treatment information, and clinical events were collected via serial surveys. Tumor and treatment data were obtained from medical record review. Five- and 10-year risks of SPNBCs were estimated via the cumulative incidence function, considering death, metastasis, or second primary BC as competing events. Fine and Gray subdistribution hazard models estimated subdistribution hazard ratios (sHRs) and 95% confidence intervals (CI) for SPNBC risk based on risk factors including demographics, germline genetics, primary BC characteristics, and treatments. RESULTS: Among 1,230 women, over a median follow-up of 10.1 years, 47 patients (4%) developed an SPNBC. Types of malignancy included melanoma (n = 10), thyroid (n = 10), ovarian (n = 4), sarcoma (n = 4), uterine (n = 3), rectal (n = 3), bladder (n = 2), cervical (n = 2), head/neck (n = 2), lung (n = 2), lymphoma (n = 2), pancreatic (n = 2), and renal (n = 1). Five and 10-year cumulative incidence were 1.4% and 3.2%, respectively. Median time between primary BC and SPNBC was 7.3 years. No patient factors, primary tumor characteristics, or treatments were statistically significantly associated with SPNBC in univariable or multivariable models. CONCLUSION: In this population, five-year cumulative incidence was higher than that reported among healthy women under 50 years of age, highlighting the importance of long-term surveillance for new non-breast cancers in young adult BC survivors.

Preoperative Risk Factors for Lymphedema in Inflammatory Breast Cancer.

BACKGROUND: Prophylactic lymphatic bypass or LYMPHA (LYmphatic Microsurgical Preventive Healing Approach) is increasingly offered to prevent lymphedema following breast cancer treatment, which develops in up to 47% of patients. Previous studies focused on intraoperative and postoperative lymphedema risk factors, which are often unknown preoperatively when the decision to perform LYMPHA is made. This study aims to identify preoperative lymphedema risk factors in the high-risk inflammatory breast cancer (IBC) population. METHODS: Retrospective review of our institution's IBC program database was conducted. The primary outcome was self-reported lymphedema development. Multivariable logistic regression analysis was performed to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during axillary lymph node dissection (ALND), number of positive lymph nodes, residual disease on pathology, and need for adjuvant chemotherapy. RESULTS: Of 356 patients with IBC, 134 (mean age: 51 years, range: 22-89 years) had complete data. All 134 patients underwent surgery and radiation. Forty-seven percent of all 356 patients (167/356) developed lymphedema. Obesity (body mass index > 30) (odds ratio [OR]: 2.7, confidence interval [CI]: 1.2-6.4, p = 0.02) and non-white race (OR: 4.5, CI: 1.2-23, p = 0.04) were preoperative lymphedema risk factors. CONCLUSION: Patients with IBC are high risk for developing lymphedema due to the need for ALND, radiation, and neoadjuvant chemotherapy. This study also identified non-white race and obesity as risk factors. Larger prospective studies should evaluate potential racial disparities in lymphedema development. Due to the high prevalence of lymphedema, LYMPHA should be considered for all patients with IBC.

Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

BACKGROUND: Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients. METHODS: The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as 'not performed/not acted on' if ALND was either not performed or performed at a later date than SLNB, or 'performed/acted on' if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT. RESULTS: Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p < 0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70-10.5; p < 0.001). CONCLUSIONS: We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.

Incidence, characteristics, and management of central nervous system metastases in patients with inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC. METHODS: The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS-free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS. RESULTS: A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1-, 2-, and 5-year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow-up: 5.6 years) and 17%, 30%, and 42% in stage IV patients (1.8 years). Multivariate analysis identified triple-negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple-negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS. CONCLUSIONS: Patients with IBC, particularly those with triple-negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted.

Optimizing Axillary Management in Clinical T1-2N0 Mastectomy Patients with Positive Sentinel Lymph Nodes.

BACKGROUND: Following publication of the AMAROS trial, we sought to optimize axillary lymph node dissection (ALND) or postmastectomy radiation therapy (PMRT) + axillary radiation (AxRT) utilization in cT1-2N0 patients with 1-2 positive sentinel lymph nodes (SLNs) after mastectomy. METHODS: In November 2015, our multidisciplinary group implemented a protocol to omit intraoperative SLN evaluation for mastectomy patients with cT1-2N0 breast cancer likely to be recommended PMRT if found to have 1-2 positive SLNs (age ≤ 60 years and/or high-risk features defined as estrogen receptor-negative and/or positive for lymphovascular invasion). We prospectively evaluated axillary management, short-term complications, and oncologic outcomes in patients with 1-2 positive SLNs. RESULTS: From November 2015 to December 2018, 479 of 560 (85%) cT1-2N0 breast cancers treated with mastectomy were potential candidates for PMRT. Intraoperative SLN evaluation was omitted in 344 (72%), thus following the protocol. Overall, 121 cases had 1-2 positive SLNs: 17 (14%) were managed with observation, 5 (4%) PMRT alone, 59 (49%) PMRT + AxRT, 16 (13%) ALND alone, and 24 (20%) ALND + PMRT. Protocol compliance resulted in less ALND (8% vs. 24%) and less ALND + PMRT (9% vs. 41%, p < 0.01). At median follow-up of 24 months, there was one regional and four distant recurrences, with no regional recurrences or differences in disease-free survival in patients treated with ALND versus PMRT + AxRT (100% vs. 98%, p = 0.67). Similarly, there were no differences in complication rates (p = 0.18). CONCLUSIONS: Omitting intraoperative SLN evaluation in cT1-2N0 mastectomy patients who would be candidates for PMRT if found to have positive nodes decreased rates of ALND and minimized use of ALND + PMRT without compromising outcomes.

Time-Driven Activity-Based Costing in Breast Cancer Care Delivery.

BACKGROUND: Accurate measurement of healthcare costs is required to assess and improve the value of oncology care. OBJECTIVES: We aimed to determine the cost of breast cancer care provision across collaborating health care organizations. METHODS: We used time-driven activity-based costing (TDABC) to calculate the complete cost of breast cancer care-initial treatment planning, chemotherapy, radiation therapy, surgical resection and reconstruction, and ancillary services (e.g., psychosocial oncology, physical therapy)-across multiple hospital sites. Data were collected between December 2019 and February 2020. TDABC steps involved (1) developing process maps for care delivery pathways; (2) determine capacity cost rates for staff, medical equipment, and hospital space; (3) measure the time required for each process step, both manually through clinic observation and using data from the Real-Time Location System (RTLS); and (4) calculate the total cost of care delivery. RESULTS: Surgical care costs ranged from $1431 for a lumpectomy to $12,129 for a mastectomy with prepectoral implant reconstruction. Radiation therapy was costed at $1224 for initial simulation and patient education, and $200 for each additional treatment. Base costs for chemotherapy delivery were $382 per visit, with additional costs driven by chemotherapy agent(s) administered. Personnel expenses were the greatest contributor to the cost of surgical care, except in mastectomy with implant reconstruction, where device costs equated to up to 60% of the cost of surgery. CONCLUSION: The cost of complete breast cancer care depended on (1) treatment protocols; (2) patient choice of reconstruction; and (3) the need for ancillary services (e.g., physical therapy). Understanding the actual costs and cost drivers of breast cancer care delivery may better inform resource utilization to lower the cost and improve the quality of care.

Utilization and predictors of postmastectomy radiation receipt in an Oncology Center in Zimbabwe.

PURPOSE: Few sub-Saharan African studies have ascertained utilization for postmastectomy radiation (PMRT) for breast cancer, the second most common cancer among African women. We estimated PMRT utilization and identified predictors of PMRT receipt in Zimbabwe. METHODS: Retrospective patient cohort included non-metastatic breast cancer patients treated from 2014 to 2019. PMRT eligibility was assigned per NCCN guidelines. Patients receiving chemotherapy for non-metastatic disease were also included. The primary endpoint was receipt of PMRT, defined as chest wall with/without regional nodal radiation. Predictors of receiving PMRT were identified using logistic regression. Model performance was evaluated using the c statistic and Hosmer-Lemeshow test for goodness-of-fit. RESULTS: 201 women with localized disease and median follow-up of 11.4 months (IQR 3.3-17.9) were analyzed. PMRT was indicated in 177 women and utilized in 59(33.3%). Insurance coverage, clinical nodal involvement, higher grade, positive margins, and hormone therapy receipt were associated with higher odds of PMRT receipt. In adjusted models, no hormone therapy (aOR 0.12, 95% CI 0.043, 0.35) and missing grade (aOR 0.07, 95% CI 0.01, 0.38) were associated with lower odds of PMRT receipt. The resulting c statistic was 0.84, with Hosmer-Lemeshow p-value of 0.93 indicating good model fit. CONCLUSION: PMRT was utilized in 33% of those meeting NCCN criteria. Missing grade and no endocrine therapy receipt were associated with reduced likelihood of PMRT utilization. In addition to practice adjustments such as increasing hypofractionation and increasing patient access to standard oncologic testing at diagnosis could increase postmastectomy utilization.

Patterns of breast reconstruction in patients diagnosed with inflammatory breast cancer: The Dana-Farber Cancer Institute's Inflammatory Breast Cancer Program experience.

Inflammatory breast cancer (IBC) exhibits dermal lymphatic involvement at presentation, and thus, the standard surgical approach is a nonskin-sparing modified radical mastectomy (MRM) without breast reconstruction (BR). In this study, we evaluated immediate and delayed BR receipt and its outcomes in IBC. Using an IRB-approved database, we retrospectively evaluated stage III IBC patients who received trimodality therapy (preoperative systemic therapy, followed by MRM and postmastectomy chest wall/regional nodal radiation). Patients with an insufficient response to preoperative systemic therapy and/or who required preoperative radiotherapy were excluded. BR receipt, timing, and morbidity were evaluated. Among 240 stage III IBC patients diagnosed between 1997 and 2016, 40 (17%) underwent BR. Thirteen (33%) had immediate, and 27 (67%) had delayed BR. Four patients had complications (1 [8%] immediate BR and 3 [11%] delayed BR); only 1 BR (delayed) was unsuccessful. From the MRM date, the median time to recurrence was 35 months (<1-212) and median overall survival was 87 months (<1-212). In this cohort of stage III IBC patients, only 11% pursued delayed BR following trimodality therapy, possibly attributable to the observed high recurrence rates hindering BR. Further studies addressing BR outcomes in IBC are needed for better counseling patients regarding their reconstructive options.

Long-term outcomes of breast-conserving therapy for women with ductal carcinoma in situ.

PURPOSE: Improved imaging, surgical techniques, and pathologic evaluation likely have decreased local recurrence rates for patients with ductal carcinoma in situ (DCIS). We present long-term outcomes of a large single-institution series after breast-conserving surgery (BCS) and adjuvant radiation therapy (RT). METHODS: We retrospectively reviewed the records of 245 women treated for DCIS with BCS and RT between 2001 and 2007. Competing risk analysis was used to calculate local recurrence (LR) as a first event with the development of a second non-breast malignancy, contralateral breast cancer, and death as competing first events. RESULTS: At a median follow-up of 10.6 years, 4 patients had a LR (2 DCIS, 2 invasive) as a first event with a cumulative LR incidence of 0.0% and 1.5% at 5 and 10 years, respectively. Most patients had > 2 mm margins (90%), specimen radiographs (93%), and received a tumor bed boost (99%). The majority (60%) of patients with hormone receptor-positive disease received adjuvant endocrine therapy. Ten-year cumulative incidence of contralateral breast cancer (CBC) was 7.9%, second non-breast malignancy was 4.5%, and death unrelated to breast cancer was 3.5%. Family history, age at diagnosis, and receipt of endocrine therapy were not significantly associated with the development of CBC (all P > 0.05). CONCLUSIONS: With mature follow-up, our rates of local recurrence following breast-conserving therapy for DCIS remain very low (1.5% at 10 years). The incidence of CBC was higher than the LR incidence. Predisposing factors for the development of CBC are worthy of investigation.

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

PURPOSE: Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T). METHODS: Patients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan-Meier method. RESULTS: Of the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4-96.2), and LRR-free survival was 98.6% (95% CI 97.4-99.8). CONCLUSION: LRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy.

Breast-cancer subtype, age, and lymph node status as predictors of local recurrence following breast-conserving therapy.

PURPOSE/OBJECTIVES: Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT. METHODS: We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models. RESULTS: With a median follow-up of 106 months, 69 LRs (3 %) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B = 3.01, HER2 = 6.29, triple-negative [TNBC] = 4.72; p < 0.001 each), younger age (HR of oldest vs. youngest quartile = 0.43; p = 0.005), regional nodal involvement (HR for 4-9 involved nodes = 3.04; >9 nodes = 5.82; p < 0.01 for each), positive margins (HR 2.43; p = 0.005), and high grade (HR 5.37; p < 0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B = 2.64, HER2 = 5.42, TNBC = 4.32; p < 0.001 for each), younger age (HR for age >50 = 0.56; p = 0.01), and nodal disease (HR 1.06 per involved node; p < 0.004) were associated with LR. The 8-year risk of LR was 2.8 % for node-negative patients and 5.2 % for node-positive patients. CONCLUSION: BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era.

The Impact of Reexcision and Residual Disease on Local Recurrence Following Breast-Conserving Therapy.

PURPOSE: Risk factors for local recurrence (LR) following breast-conserving therapy (BCT) inform the need for local therapy. A Danish population-based cohort study identified residual disease on reexcision as an independent risk factor for LR but was limited by incomplete data on biologic subtype (Bodilsen et al. 2015 in Ann Surg Oncol 22: S476-S485). We sought to elaborate this risk in an independent cohort with clearly defined biologic subtypes. METHODS: The study population included patients with localized invasive breast cancer with complete biologic subtype data treated with BCT with one or zero reexcisions at one institution from 1998 to 2008. Cumulative incidence of LR was calculated using competing risk analysis, and associated risk factors were evaluated using Cox proportional hazards regression. RESULTS: A total 1073 consecutive patients were included with a median follow-up of 10 years. The 10-year LR rates were 2.4% [95% confidence interval (CI) 1.4-3.9%] without reexcision, 6.0% (95% CI 3.8-8.9%) with reexcision, and 8.2% (95% CI 4.1-14.0%) with any reexcised residual disease. On univariate regression, residual disease [hazard ratio (HR) = 1.50, p = 0.31] was not significantly associated with LR. Subtype other than luminal A/luminal-HER2 (luminal B HR = 2.29, p = 0.033; HER2/triple-negative HR = 2.85, p = 0.004), age (HR = 0.95 per year, p < 0.001), and nodal involvement (HR = 1.12 per involved node, p = 0.001) remained significant on multivariate regression. The impact of residual disease was confounded by its association (p < 0.001) with nodal involvement. CONCLUSIONS: Our findings suggest that LR is associated with younger age, nodal involvement, and biologic subtype but not with residual disease at reexcision. The study's power is limited by the low incidence of LR despite detailed clinical data and long-term follow-up. Further study is required.

The Impact of Residual Disease After Preoperative Systemic Therapy on Clinical Outcomes in Patients with Inflammatory Breast Cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease treated with multimodality therapy: preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM), chest wall and regional nodal radiotherapy, and adjuvant biologic therapy and/or endocrine therapy when appropriate. In non-IBC, the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if pathologic response correlates with oncologic outcomes of IBC patients. METHODS: Following review of IBC patients' records (1997-2014), we identified 258 stage III IBC patients; 181 received PST followed by MRM and radiotherapy and were subsequently analyzed. Pathologic complete response (pCR) to PST, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, grade, and histology were evaluated as predictors of TTR and OS by Cox model. RESULTS: Overall, 95/181 (52%) patients experienced recurrence; 93/95 (98%) were distant metastases (median TTR 3.2 years). Seventy-three patients (40%) died (median OS 6.9 years). pCR was associated with improved TTR (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.09-0.46, p < 0.01, univariate; HR 0.17, 95% CI 0.07-0.41, p < 0.0001, multivariate) and improved OS (HR 0.26, 95% CI 0.11-0.65, p < 0.01, univariate). In patients with pCR, grade III (HR 1.91, 95% CI 1.16-3.13, p = 0.01), and triple-negative phenotype (HR 3.54, 95% CI 1.79-6.98, p = 0.0003) were associated with shorter TTR, while residual ductal carcinoma in situ was not (HR 0.85, 95% CI 0.53-1.35, p = 0.48, multivariate). CONCLUSIONS: In stage III IBC, pCR was associated with prognosis, further influenced by grade, hormone receptor, and HER2 status. Investigating mechanisms that contribute to better response to PST could help improve oncologic outcomes in IBC.

Body Mass Index and Locoregional Recurrence in Women with Early-Stage Breast Cancer.

BACKGROUND: Higher body mass index (BMI) has been associated with increased distant recurrence and decreased survival for women with breast cancer. However, the relationship between BMI and locoregional recurrence (LRR) has been less well studied and was therefore the subject of this investigation. METHODS: The study identified 878 women with early-stage invasive breast cancer who underwent breast-conservation therapy (BCT) between June 1997 and October 2007. Time from diagnosis to LRR was calculated using a competing risk analysis with contralateral breast cancer (CBC), distant metastases (DM), and death as the competing risks. Gray's competing risks analysis, which included an interaction term between menopausal status and BMI, was used to identify significant risk factors for the development of LRR. RESULTS: After a median follow-up period of 10.8 years, LRR was diagnosed as a first event for 45 women. In a multivariable analysis, BMI was positively associated with LRR but only in premenopausal women. Specifically, when these women were compared with normal- and underweight women, both the overweight women (hazard ratio (HR), 2.97; 95 % confidence interval (CI) 1.04-8.46; p = 0.04) and the obese women (HR, 3.36; 95 % CI 1.07-10.63; p = 0.04) showed a higher risk of LRR. A similar association between BMI and disease-free survival was noted for premenopausal but not postmenopausal women. CONCLUSION: For premenopausal women with invasive breast cancer who undergo BCT, BMI is an independent prognostic factor for LRR. If confirmed, these findings suggest that more aggressive treatment strategies may be warranted for these women.

Immediate breast reconstruction following mastectomy in pregnant women with breast cancer.

BACKGROUND: Surgical management of breast cancer in pregnancy (BCP) requires balancing benefits of therapy with potential risks to the developing fetus. Minimal data describe outcomes after mastectomy with immediate breast reconstruction (IR) in pregnant patients. METHODS: Retrospective review was performed of patients who underwent IR after mastectomy within a BCP cohort. Parameters included intra- and post-operative complications, short-term maternal/fetal outcomes, surgery duration, and delayed reconstruction in non-IR cohort. RESULTS: Of 82 patients with BCP, 29 (35%) had mastectomy during pregnancy: 10 (34%) had IR, 19(66%) did not. All IR utilized tissue expander (TE) placement. Mean gestational age (GA) at IR was 16.2 weeks. Mean surgery duration was 198 min with IR versus 157 min without IR. Those with IR delivered at, or close to, term infants of normal birthweight. No fetal or major obstetrical complications were seen. Post-mastectomy radiation (PMRT) was provided after pregnancy in 2 (20%) patients in the IR cohort and 12 (63%) in the non-IR cohort. All patients in the IR cohort successfully transitioned to permanent implant. CONCLUSIONS: This report represents one of the largest series describing IR during BCP. IR after mastectomy increased surgery duration, but was not associated with adverse obstetrical or fetal outcomes. IR with TE may preserve reconstructive options when PMRT is indicated. J. Surg. Oncol. 2016;114:140-143. © 2016 Wiley Periodicals, Inc.