El papel de la nutrición en la génesis del cáncer de mama / Nutrition in breast cancer genesis

El cáncer de mama es el tumor más prevalente en las mujeres y ocupa el primer lugar en incidencia y en mortalidad en muchos países. Si bien las causas del cáncer de mama son complejas y multifactoriales, los factores nutricionales y aquellos relacionados con el estado nutricional juegan un papel importante en el desarrollo de la enfermedad. De esta forma, se han identificado algunos factores que aumentan su riesgo, como el aumento de peso, la cantidad de tejido adiposo, la circunferencia de cintura, el consumo de alcohol, etc., o bien, que lo reducen, como el consumo de frutas y verduras. Los factores nutricionales o que dependen del estado de nutrición son modificables y prevenibles, por lo que deben tenerse en cuenta al diseñar programas de prevención eficaces. (AU)

Breast cancer is the most prevalent tumor in women, ranking first in incidence and mortality in many countries. Although the causes of breast cancer are complex and multifactorial, nutritional factors and those related to nutritional status play an important role in the development of the disease. In this way, factors that increase breast cancer risk have been identified, such as weight gain, the amount of adipose tissue, waist circumference, alcohol consumption or the consumption of red meat and processed meat, while other factors have been identified that reduce the risk, such as eating fruits and vegetables. Nutritional factors or factors that depend on the state of nutrition are modifiable and preventable, so they must be considered when designing effective prevention programs. (AU)

Intraoperative irradiation in breast cancer: preliminary results in 80 patients as partial breast irradiation or anticipated boost prior to hypo-fractionated whole breast irradiation

PurposeTo present the first results of intraoperative irradiation (IORT) in breast cancer with a low-energy photon system used as partial breast irradiation (PBI) or as an anticipated boost before whole breast hypo-fractionated irradiation (IORT + WBI), concerning tolerance, side effects, quality of life, and patient-reported outcomes.Materials and methodsEighty patients treated with an Intrabeam® system of 50 kV X-rays received a 20 Gy dose intraoperatively were included. Moderate daily hypofractionation of 2.7 Gy in 15 fractions up to 40.5 Gy was administered if high-risk factors were present. Acute post-operative toxicity, surgery complications, chronic toxicity, patient-reported cosmesis and Breast-Q questionnaire were performed at follow-up visits.ResultsThirty-one patients were treated as PBI and the remaining 49 as IORT + WBI. Only the IORT + WBI group presented acute toxicity, mainly mild acute dermatitis (11 patients) and one subacute mastitis. A total of 20 patients presented fibrosis (18 patients grade I, 2 patients grade II), 15 (30.5%) patients in the IORT + WBI group and 3 (9.6%) patients in the group of PBI. The cosmesis evaluation in 73 patients resulted poor, fair, good or excellent in 2, 7, 38 and 26 patients, respectively. In PBI group Breast-Q scored higher, especially in terms of their psychosocial well-being (78 vs 65) and satisfaction with radiation-induced toxicity (77 vs 72, respectively) compared to IORT + WBI group.ConclusionIORT is a well-tolerated procedure with low toxicity, good cosmesis and favorable patient-reported outcomes mainly when administered as PBI.

Adjuvant radiotherapy did not increase the risk of coronary heart disease in patients with non-metastatic breast cancer.

OBJECTIVE: Adjuvant radiotherapy (RT) in patients with breast cancer can adversely cause the heart to receive some radiation doses, which may lead to cardiovascular diseases. The results of previous research regarding this issue are not consistent. Therefore, we conducted a nationwide population-based study in Taiwan to evaluate whether adjuvant RT for breast cancer patients increased the risk of developing coronary heart disease (CHD). METHODS: This retrospective cohort study examined data from the National Health Insurance Research Database, Registry for Catastrophic Illness Patients, and Taiwan Cancer Registry Database. We identified 83,733 patients with breast cancer between 1 January 2000 and 31 December 2017. Individuals without breast cancer from the general population were frequency-matched by age and index year with individuals with breast cancer. Participants were followed until the occurrence of a CHD event, the end of follow-up, or patient record removal due to death or withdrawal from the NHI. A Cox proportional hazards regression analysis was conducted to compare the risk of CHD in breast cancer patients with that in patients in the comparison cohort. RESULTS: Compared to breast cancer patients without RT, those who underwent RT had a similar risk of subsequently developing CHD (adjusted hazard ratio, 0.94; 95% confidence interval, 0.87-1.02). Similar results were observed in a subgroup of patients with left-sided breast cancer. However, among patients who received adjuvant RT, those with left-sided breast cancer had a significantly higher risk of CHD than did those with right-sided breast cancer (adjusted hazard ratio, 1.17; 95% confidence interval, 1.04-1.30). Patients who received RT in 2010 or later had a significantly lower risk of CHD compared with those who received RT before 2010 (adjusted hazard ratio, 0.64; 95% confidence interval, 0.45-0.91). Higher prescribed doses of RT to the left-sided breast did not correspond to a higher risk of CHD. CONCLUSION: This large, nationwide cohort study suggests that adjuvant RT in patients with breast cancer did not increase the risk of CHD.

Angiosarcoma associated with radiation therapy after treatment of breast cancer. Retrospective study on ten years.

PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.

Secondary cancer risk after whole-breast radiation therapy: field-in-field versus intensity modulated radiation therapy versus volumetric modulated arc therapy.

OBJECTIVE: In this study, we used the concept of organ-equivalent dose (OED) to evaluate the excess absolute risk (EAR) for secondary cancer in various organs after radiation treatment for breast cancer. METHODS: Using CT data set of 12 patients, we generated three different whole-breast radiation treatment plans using 50 Gy in 2 Gy fractions: three-dimensional conformal radiotherapy with a field-in-field (FinF) technique, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). The OEDs were calculated from differential dose-volume histograms on the basis of the "linear-exponential," "plateau," and "full mechanistic" dose-response models. Secondary cancer risks of the contralateral breast (CB), contralateral lung (CL), and ipsilateral lung (IL) were estimated and compared. RESULTS: The lowest EARs for the CB, CL, and IL were achieved with FinF, which reduced the EARs by 77%, 88%, and 56% relative to those with IMRT, and by 77%, 84%, and 58% relative to those with VMAT, respectively. The secondary cancer risk for FinF was significantly lower than those of IMRT and VMAT. OED-based secondary cancer risks for CB and IL were similar when IMRT and VMAT were used, but the risk for CL was statistically lower when VMAT was used. CONCLUSION: The overall estimation of EAR indicated that the radiation-induced cancer risk of breast radiation therapy was lower with FinF than with IMRT and VMAT. Therefore, when secondary cancer risk is a major concern, FinF is considered to be the preferred treatment option in irradiation of whole-breast. ADVANCES IN KNOWLEDGE: Secondary malignancy estimation after breast radiotherapy is becoming an important subject for comparative treatment planning.When secondary cancer risk a major concern, FinF technique is considered the preferred treatment option in whole breast patients.

Is Multifocal Regression a Risk Factor for Ipsilateral Breast Tumor Recurrence in the Modern Era After Neoadjuvant Chemotherapy and Breast Conservation Therapy?

PURPOSE: Multifocal pattern of regression after neoadjuvant chemotherapy has been identified as a risk factor for ipsilateral breast tumor recurrence (IBTR). We aimed to determine the significance of multifocal regression as a predictor of IBTR after neoadjuvant chemotherapy and breast conservation therapy in the modern era. METHODS AND MATERIALS: We retrospectively reviewed 346 patients treated between November 2009 and June 2017. Pattern of regression was categorized as pathologic complete response (pCR), unifocal (tumor present as a cohesive mass), limited multifocal (single cells or clusters of cells concentrated in 1 portion of the fibrotic area), or diffuse multifocal (cells spread over entire fibrotic area). IBTR was defined as new ipsilateral invasive or noninvasive breast tumor after breast conservation therapy. Predictive factors were analyzed using Cox regression. RESULTS: Incidence of multifocal regression was 25.7% for the overall cohort and 12.2% for estrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER2) positive, 17.5% for triple-negative, 36.9% for ER+ or PR+/HER2-, and 38.5% for triple-positive (P < .001). With a median follow-up of 41.1 months, 4-year IBTR-free survival after pCR or unifocal regression versus multifocal regression was 94.1% versus 90.9% (P = .411). Pattern of regression (P = .010; compared to pCR, hazard ratio [HR] of 11.2 for diffuse multifocal regression, 1.65 for limited multifocal regression, and 3.81 for unifocal regression), phenotype (P = .001; compared to ER+ or PR+/HER2-, HR of 30.67 for ER-/PR-/HER2+, 25.30 for triple-negative, and 1.60 for triple-positive), and lack of nodal pCR (P = .004; HR of 3.78) predicted for IBTR on multivariate Cox regression. On multivariate subset analysis, pattern of regression and lymphovascular space invasion predicted for IBTR in hormone receptor-negative patients, but pattern of regression was not associated with IBTR for hormone receptor-positive patients. CONCLUSIONS: Multifocal regression, hormone receptor-negative phenotype, and lack of nodal pCR predict for increased risk of IBTR after neoadjuvant chemotherapy. Although more common in hormone receptor-positive disease, multifocal regression was associated with worse outcome only in hormone receptor-negative patients.

Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer.

Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non-BRCA mutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows: BRCA carriers (42.3%), non-BRCA carriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non-BRCA carriers and BRCA carriers (P = 0.6205). Among non-BRCA carriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM between BRCA carriers and non-BRCA carriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non-BRCA carriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election among BRCA carriers, non-BRCA carries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non-BRCA genes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.

Critical Appraisal of the Risk of Secondary Cancer Induction From Breast Radiation Therapy With Volumetric Modulated Arc Therapy Relative to 3D Conformal Therapy.

PURPOSE: To evaluate the excess absolute risk (EAR) comparing volumetric modulated arc therapy (VMAT) and 3-dimensional (3D) conformal radiation therapy (CRT) in breast cancer radiation therapy treatment. METHODS AND MATERIALS: Two VMAT arrangements (VMAT_tang and VMAT_full, i.e. partial arcs with and without a sector of 0 Monitor Unit, respectively) and a 3D CRT (field-in-field [FinF]) plan were calculated with an accurate dose calculation algorithm, Acuros, in 20 patients presenting with early-stage breast cancer. The dose prescription was 40.05 Gy in 15 fractions. The planning aim was to maximize the dose reduction in the lungs, contralateral breast, heart, and coronary artery. EAR was estimated using different models: linear, linear-exponential, plateau, and full model, which better uses a carcinogenesis model and epidemiologic data for carcinoma induction and which accounts for cell repopulation or repair during the radiation therapy dose fractionation. EAR was computed for contralateral structures-breast and lung-as well as the ipsilateral lung. Normal tissue complication probability (NTCP) was computed to estimate the ipsilateral lung, heart, and skin toxicity, to balance with respect to second cancer induction. RESULTS: The planning objectives were fulfilled with all the planning techniques. EAR for contralateral breast carcinoma induction, estimated with the most accurate model, was 1.7, 2.4, and 8.5 (per 10,000 patients per year) with FinF, VMAT_tang, and VMAT_full, respectively. For the contralateral lung, these figures were 1.5, 1.6, and 7.3 (per 10,000 patients per year), respectively. NTCP for all the analyzed endpoints was significantly higher with FinF relative to both VMAT settings, with VMAT_full presenting the lowest toxicity risk. CONCLUSIONS: VMAT, in particular with the VMAT_tang setting, could have the same risk of second cancer induction as 3D CRT delivered with the FinF setting for the contralateral organs while reducing acute and late NTCP for the ipsilateral organs. VMAT might be considered a safe technique for breast cancer treatment for those aspects.