Boughey, Judy C.

Abstract Background Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort. Methods Patients with non-metastatic IBC treated in 2010–2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−), ER−/HER2− and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan–Meier curves and Cox proportional hazards regression to analyse overall survival. Results Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2− in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER−/HER2− in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2− (6·2 per cent), HER2+ (38·8 per cent), ER−/HER2− (19·1 per cent) (P < 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2− 64·9 per cent, HER2+ 74·0 per cent, ER−/HER2− 44·0 per cent; P < 0·001) and by pCR within subtypes (all P < 0·001). In multivariable analysis, ER−/HER2− subtype (hazard ratio 2·89 versus HER2+ as reference; P < 0·001) and absence of total pCR (hazard ratio 3·23; P < 0·001) predicted worse survival. Conclusion Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.

PURPOSEThe phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin is a key pathway of survival and therapeutic resistance in breast cancer. We evaluated the pan-Akt inhibitor MK-2206 in combination with standard therapy in patients with high-risk early-stage breast cancer.PATIENTS AND METHODSI-SPY 2 is a multicenter, phase II, open-label, adaptively randomized neoadjuvant platform trial that screens experimental therapies and efficiently identifies potential predictive biomarker signatures. Patients are categorized by human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and MammaPrint statuses in a 2 × 2 × 2 layout. Patients within each of these 8 biomarker subtypes are adaptively randomly assigned to one of several experimental therapies, including MK-2206, or control. Therapies are evaluated for 10 biomarker signatures, each of which is a combination of these subtypes. The primary end point is pathologic complete response (pCR). A therapy graduates with one or more of these signatures if and when it has an 85% Bayesian predictive probability of success in a hypothetical phase III trial, adjusting for biomarker covariates. Patients in the current report received standard taxane- and anthracycline-based neoadjuvant therapy without (control) or with oral MK-2206 135 mg/week.RESULTSMK-2206 graduated with 94 patients and 57 concurrently randomly assigned controls in 3 graduation signatures: HR-negative/HER2-positive, HR-negative, and HER2-positive. Respective Bayesian mean covariate-adjusted pCR rates and percentage probability that MK-2206 is superior to control were 0.48:0.29 (97%), 0.62:0.36 (99%), and 0.46:0.26 (94%). In exploratory analyses, MK-2206 evinced a numerical improvement in event-free survival in its graduating signatures. The most significant grade 3-4 toxicity was rash (14% maculopapular, 8.6% acneiform).CONCLUSIONThe Akt inhibitor MK-2206 combined with standard neoadjuvant therapy resulted in higher estimated pCR rates in HR-negative and HER2-positive breast cancer. Although MK-2206 is not being further developed at this time, this class of agents remains of clinical interest.

Background: Prepectoral implant-based breast reconstruction has gained popularity because of advantages over the subpectoral technique. Acellular dermal matrix use with implant-based breast reconstruction has become common because of its perceived superior aesthetic outcome. Matrices are expensive, however, and recent evidence has pointed to several potential complications. This article reports a series of prepectoral implant-based breast reconstructions with and without acellular dermal matrix and compared their outcomes. Methods: This is a single-surgeon retrospective review of patients who underwent staged prepectoral implant-based breast reconstruction following nipple-sparing mastectomy over two periods. Patients with well-perfused mastectomy skin flaps with a homogeneous thickness underwent reconstruction with acellular dermal matrix initially. On evolution of the practice, it was not used. Patient demographics, operative data, and complications were analyzed. Aesthetic outcome was measured by the BREAST-Q survey and the Aesthetic Item Scale. A cost analysis was also performed. Results: Forty patients were included (acellular dermal matrix group, n = 19; non–acellular dermal matrix group, n = 21). The nonmatrix group had one case (5 percent) of seroma and one case (5 percent) with hematoma; there were none in the acellular dermal matrix group. Average BREAST-Q and Aesthetic Item Scale scores were 82.3 versus 81.6 (p = 0.954) and 20.98 versus 20.43 (p = 0.640) for the matrix and nonmatrix groups, respectively. The direct cost savings for the authors’ institution over 1 year if matrix was not used in all cases of implant-based breast reconstruction would be estimated at $3,105,960 to $6,211,920 for unilateral and bilateral cases, respectively, for Medicare reimbursement. Conclusions: With adequate patient selection, acellular dermal matrix is not always required during two-stage prepectoral implant-based breast reconstruction for good aesthetic outcomes. The economic burden on patients and the health care system could be lessened with selective matrix use. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Background: The authors compared long-term health care use and cost in women undergoing immediate autologous breast reconstruction and implant-based breast reconstruction. Methods: This study was conducted using the OptumLabs Data Warehouse, which contains deidentified retrospective administrative claims data, including medical claims and eligibility information from a large U.S. health insurance plan. Women who underwent autologous or implant-based breast reconstruction between January of 2004 and December of 2014 were included. The authors compared 2-year use rates and predicted costs of care. Comparisons were tested using the t test. Results: Overall, 12,296 women with immediate breast reconstruction were identified; 4257 with autologous (35 percent) and 8039 with implant-based (65 percent) breast reconstruction. The proportion of autologous breast reconstruction decreased from 47.2 percent in 2004 to 32.7 percent in 2014. The mean predicted reconstruction cost of autologous reconstruction was higher than that of implant-based reconstruction in both unilateral and bilateral surgery. Similar results for mean predicted 2-year cost of care were seen in bilateral procedures. However, in unilateral procedures, the 2-year total costs were higher for implant-based than for autologous reconstruction. Two-year health care use rates were higher for implant-based reconstruction than for autologous reconstruction for both unilateral and bilateral procedures. Women undergoing unilateral implant-based reconstruction had higher rates of hospital admissions (30.3 versus 23.1 per 100; p < 0.01) and office visits (2445.1 versus 2283.6 per 100; p < 0.01) than those who underwent autologous reconstruction. Emergency room visit rates were similar between the two methods. Bilateral procedures yielded similar results. Conclusion: Although implant-based breast reconstruction is a less expensive index operation than autologous breast reconstruction, it was associated with higher health care use, resulting in similar total cost of care over 2 years.

Background National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community. Methods Patients with stage II to III gastric adenocarcinoma undergoing curative‐intent resection (National Cancer Data Base, 2006‐2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan‐Meier analysis was used to assess survival. Results There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10‐year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline‐concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values <.001). The median overall survival was 45.5 months for patients who received guideline‐concordant care and 32.0 months for those who did not ( P < .001, reference for all ORs: academic programs). Conclusions Compliance with guidelines was associated with improved outcomes. Although the rate of compliance with NCCN guidelines is improving, integrated care networks may be an important way of improving the quality of gastric cancer care within the community.

Abstract Breast cancer survivorship guidelines recommend at least annual follow-up visits, yet the degree to which this occurs in clinical practice is uncertain. Claims data from a US commercial insurance database (OptumLabs) were used to identify women treated with curative intent surgery for newly diagnosed breast cancer between 2006 and 2014. In 25 035 women, median follow-up was 3 years. In the second year after surgery, 9.6% of the patients did not visit a primary care provider, an oncologist, or a surgeon (guideline-nonadherent). The guideline-nonadherent proportion increased from 7.8% in women diagnosed in 2006 to 12.2% in those diagnosed in 2014 (two-sided Wald P &lt; .001). During years 2–6, guideline-nonadherence was also associated with older age, nonwhite race, no radiation, no chemotherapy, no endocrine therapy, and increasing time after surgery. There is a substantial and increasing rate of inadequate follow-up among breast cancer survivors. This has the potential to impair outcomes.

Background Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors. Methods Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan‐Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors. Results A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast‐conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor–positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node–negative, estrogen receptor–positive/human epidermal growth factor receptor 2 (HER2)‐negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy ( P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor–positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival. Conclusions Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research.

Background: Breast cancer diagnosis and treatment affect quality of life and stress and are associated with fatigue. Meditation interventions are effective strategies for patients with breast cancer but are often limited by poor access, high cost, substantial time commitment, and poor adherence. In this feasibility study, we investigated the use of a portable, wearable, electroencephalographic device for guided meditation practices by breast cancer patients during the period from breast cancer diagnosis until 3 months after surgical treatment. Methods: We enrolled women (age = 20-75 years) who had received a recent diagnosis of breast cancer and planned to undergo surgical treatment. Participants were randomly assigned to perform guided meditation with the device (intervention group) or receive CD-based stress-reduction education (control group). Surveys were used to measure stress, quality of life, and fatigue at baseline, within 4 days before surgery, up to 14 days after surgery, and at 3 months after surgery. Results: In the intervention group, 15 of 17 participants (88.2%) completed the study; in the control group, 13 of 13 participants completed the study (100%). Participants in both groups had less fatigue and stress and improved quality of life at 2 weeks and 3 months after surgery compared with baseline, but there were no significant intergroup differences at any time point. Conclusion: The use of this wearable electroencephalographic device for meditation is a feasible strategy for patients with breast cancer.