The Impact of Obesity on Breast Cancer Argolo, Daniel F.; Hudis, Clifford A.; Iyengar, Neil M.
Current oncology reports,
06/2018, Letnik:
20, Številka:
6
Journal Article
Recenzirano
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.
Obesity and Cancer: Concepts and Challenges Argolo, Daniel F.; Iyengar, Neil M.; Hudis, Clifford A.
Indian journal of surgical oncology,
12/2015, Letnik:
6, Številka:
4
Journal Article
Recenzirano
Odprti dostop
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.
Obesity is a major global health problem with a rising worldwide burden. In addition to its association with several diseases, obesity is associated with increased incidence and worse prognosis for ...many malignances. Many possible mechanisms that contribute to the obesity-cancer link have been proposed, but key pathways likely include steroid hormone signaling, altered gut microbiota, insulin and insulin growth factor interactions, levels of circulating adipokines, and local and systemic inflammation. By understanding these mechanisms and their interactions, we may be able to intervene to improve the public health burden imposed by obesity. Equally critical to the development of targeted intervention strategies is the identification of accurate biomarkers to better detect populations that are more or less likely to benefit from specific interventions.
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.
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 + 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.
This study evaluates, for the first time, the role of doxorubicin and cyclophosphamide followed by paclitaxel and dual anti‐HER2 therapy with trastuzumab and pertuzumab in patients with early stage HER2‐positive breast cancer.
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