The rates of obesity are increasing worldwide and this condition is now recognized as a leading preventable cause of cancer. Several diseases are directly related to obesity, including diabetes, hypertension, atherosclerosis, stroke, musculoskeletal disorders, and a diverse range of malignances-such as breast cancer. Obesity is associated with an increased risk of postmenopausal estrogen receptor-positive breast cancer and worse cancer-related outcomes for all breast tumor subtypes. Several mechanisms have been proposed to contribute to the obesity-cancer link, including high levels of circulating and local estrogens, altered amounts of adipokines (leptin and adiponectin), disrupted insulin/IGF signaling, modifications within the microbiome, and local and systemic effects of inflammation. Here we will review recent advances in our understanding of the complex signaling pathways underlying the obesity-cancer link. An improved understanding of these processes is anticipated to propel novel and effective intervention strategies to reduce the global obesity-cancer burden.

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Objectives. Trastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 -positive patients. A retrospective analysis was performed of patients treated with dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported.Methods. An electronic medical record review was conducted of patients treated with HP-based therapy in the neoadjuvant setting from September 1, 2013, to March 1, 2015. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as total (tpCR, ypT0/is ypN0), German Breast Group (GBG) pCR (ypT0 ypN0), breast pCR (bpCR) with in situ disease (ypT0/is) and without in situ disease (ypT0), and explored axillary pCR (ypN0). Results. Charts from 66 patients were reviewed, and 57 patients were evaluable for pCR. Median age was 46 years (range 26-68 years). Median tumor size was 4 cm. Of 57 patients, 53 (93%) had operable breast cancer (T1-3, N0-1, M0). Three patients (5.3%) had locally advanced disease (T2-3, N2-3, M0 or T4a-c, any N, M0), and 1 (1.7%) had inflammatory breast cancer (T4d, any N, M0). Overall, 44 (77%) and 13 (23%) had hormone receptor (HR)-positive and negative diseases, respectively. Median numbers of cycles of neoadjuvant treatment were as follows: AC (4, range 1-4), T (4, range 1-4), trastuzumab (6, range 3-8), and pertuzumab (6, range 2-8). In these 57 patients, the rates of tpCR and bpCR with in situ disease were demonstrated in 41/57 (72%) patients, and the rates of GBG pCR and bpCR without in situ disease were found in 30/57 (53%) patients. Of 26 patients with biopsy-proven lymph nodal involvement, axillary pCR occurred in 22 (85%) patients. Conclusion. At a single center, the tpCR and GBG pCR rates of dd AC followed by THP are high at 72% and 53%, respectively. The Oncologist 2017;22:139-143 Implications for Practice: This is the first study describing the role of doxorubicin and cyclophosphamide followed by paclitaxel and dual anti-HER2 therapy with trastuzumab and pertuzumab (ACTHP) in patients with early stage HER2-positive breast cancer. Total (breast 1 lymph node) pathological complete remission (pCR) remission (ypT0/is ypN0) and German Breast Group pCR rates (ypT0/ ypN0) were high at 72% and 53%, respectively, with the ACTHP regimen. Rate of axillary clearance in patients with known axillary involvement was high at 85%, which may translate into less extensive axillary surgeries in this subset in the future.

We previously reported progression-free survival (PFS) results on a phase II trial of weekly paclitaxel, trastuzumab, and pertuzumab in patients with human epidermal growth factor receptor 2(HER2)–positive metastatic breast cancer (MBC) treated in the first- and second-line setting. Here, we report results for overall survival (OS) and updated PFS after an additional year of follow-up. Patients with HER2-positive MBC with 0–1 prior treatment were eligible. Treatment consisted of paclitaxel (80 mg/m2) weekly, and trastuzumab (loading dose 8 mg/kg → 6 mg/kg) and pertuzumab (loading dose 840 mg → 420 mg) every 3 weeks, all given intravenously. Primary endpoint was 6-month PFS. Secondary endpoints included median PFS, 6-month and median OS. Evaluable patients received at least one full dose of treatment. From January 2011 to December 2013, 69 patients were enrolled: 51 (74 %) and 18 (26 %) treated in first- and second-line metastatic settings, respectively. As of July 1, 2015, the median follow-up was 33 months (range 3–49 months; 67 patients were evaluable for efficacy). The median OS was 44 months (95 % CI 37.5–NR) overall and 44 months (95 % CI 38.3–NR) and 37.5 months (95 % CI 30.3–NR) for patients with 0 and 1 prior metastatic treatment, respectively; 6-month OS was 98 % (95 % CI 90-1). The 6-month PFS was 86 % (95 % CI 75–93) overall and 89 % (95 % CI 76–95) and 78 % (95 % CI 51–91) for patients with 0 and 1 prior therapy, respectively; and median PFS was 21.4 months (95 % CI 14.1–NR) overall and 25.7 months (95 % CI 14.1–NR) and 16.9 months (95 % CI 8.5–NR) for patients with 0–1 prior treatment, respectively. Treatment was well tolerated. Updated analysis demonstrates that weekly paclitaxel, when added to trastuzumab and pertuzumab, is associated with a favorable OS and PFS and offers an alternative to docetaxel-based therapy. http://www.ClinicalTrials.gov NCT0127604

The rates of overweight and obesity are increasing worldwide in both developed and developing countries. Obesity is a major public health problem as it is associated with many diseases, including diabetes, hypertension, dyslipidemia, atherosclerosis, and some types of cancer. Breast cancer is a malignancy in which both the risk of development and the prognosis are negatively impacted by the obese state. The precise mechanisms pathophysiologically linking obesity and cancer are still under investigation. The biological basis for these associations includes both systemic and local tissue effects and white adipose tissue inflammation appears to be a critical component. A comprehensive understanding of the mechanisms linking obesity, inflammation and cancer may provide an opportunity for the development of strategies to attenuate the negative impact of obesity.

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The published online version contains mistake on the corresponding author's family name. The correct family name should be Argolo, not Argol. The corrected family name is shown in the author group (above) and affiliation section (below).The online version of the original article can be found at http://dx

Background: Dual anti-HER2 blockade with trastuzumab and pertuzumab (HP) plus chemotherapy is an effective therapy (Rx) in the 1st-line setting for HER2-positive metastatic breast cancer (MBC). Our single arm phase II study included patients (pts) treated with HP plus paclitaxel in the 2nd-line setting with progression-free survival (PFS) benefit. Recently, we reported results from a retrospective study of pts treated at our institution, suggesting a longer PFS for those who received HP-based Rxs when compared to any other anti-HER2 based Rxs in the 2nd-line setting. To further assess the activity of this combination in later Rx lines, we conducted a retrospective analysis of pts with HER2-positive MBC who had progressive disease after 2nd-line and were treated with HP-based Rxs in the 3rd and later lines at MSKCC. Historically, the median (med) PFS in this setting with trastuzumab-based Rx is about 3-4 months. Methods: Pts diagnosed with HER2-positive MBC and treated with HP-based Rxs at MSKCC between 1-1-2011 and 03-30-2015 and who progressed on 2nd-line Rx were identified through an institutional database. Primary endpoint was PFS in 3rd and later treatment lines. Results: 70 pts who received any HP-based Rx in the 3rd or later lines of treatment were eligible. The med number of prior anti-HER2 Rx was 3. The baseline characteristics and Rxs are summarized in Table 1. The med PFS for the entire cohort was 5.7 months (95% CI, 4.8-6.5). Conclusions: In this retrospective analysis involving heavly pretreated patients, HP-based Rx appears to be an active regimen and compares favorably to historical data. This supports the NCCN endorsement of HP-based Rx in later lines if HP has not been delivered previously. Baseline Characteristics and treatments (n=70)Characteristic(n)(%)Age  Median56 Range27-83 Gender  Female70100.0Male00.0Race  Black1014.3White5477.1Other68.6Ethnicity  Non Hispanic6694.3Hispanic45.7ER/PR status  ER and PR negative2738.6ER and/or PR positive4361.4Type of disease  Non visceral1622.9Visceral5477.1Visceral CNS2130.0Anti-HER2 in early stage  Yes2941.4No4158.6Line of therapy  3rd line1927.14th line1521.45th line912.96th line912.97th line811.48th line and beyond1014.3HP-based regimens  Chemotherapy + HP5477.1Endocrine therapy + HP57.1HP alone912.9Other22.9 Citation Format: Argolo D, Friedman M, Smyth L, Iyengar N, Singh J, Patil S, Norton L, Baselga J, Hudis C, Dang C. Activity of HP-based therapies as third and later lines for the treatment of HER2-positive metastatic breast cancer: A retrospective study from a single institution. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-20.