Adjuvant radiotherapy and risk of contralateral breast cancer.

BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life.     

Risk of treatment-related esophageal cancer among breast cancer survivors

BackgroundRadiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use.DesignNested case–control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records.ResultsThe largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P_trend < 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7–28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2–0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking).ConclusionsEsophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.     

The risk of contralateral breast cancer: a SEER-based analysis

Background We sought to estimate the annual risk and 25-year cumulative risk of contralateral breast cancer among women with stage 0–III unilateral breast cancer.Methods We identified 812,851 women with unilateral breast cancer diagnosed between 1990 and 2015 in the SEER database and followed them for contralateral breast cancer for up to 25 years. Women with a known bilateral mastectomy were excluded. We calculated the annual risk of contralateral breast cancer by age at diagnosis, by time since diagnosis and by current age. We compared risks by ductal carcinoma in situ (DCIS) versus invasive disease, by race and by oestrogen receptor (ER) status of the first cancer.Results There were 25,958 cases of contralateral invasive breast cancer diagnosed (3.2% of all patients). The annual risk of contralateral breast cancer over the 25-year follow-up period was 0.37% and the 25-year actuarial risk of contralateral invasive breast cancer was 9.9%. The annual risk varied to a small degree by age of diagnosis, by time elapsed since diagnosis and by current age. The 25-year actuarial risk was similar for DCIS and invasive breast cancer patients (10.1 versus 9.9%). The 25-year actuarial risk was higher for black women (12.7%) than for white women (9.7%) and was lower for women with ER-positive breast cancer (9.5%) than for women with ER-negative breast cancer (11.2%).Conclusions Women with unilateral breast cancer experience an annual risk of contralateral breast cancer ~0.4% per year, which persists over the 25-year follow-up period.Subject terms: Breast cancer, Cancer epidemiology     

Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer

BackgroundWomen who carry germ-line mutations in BRCA1/2 are at very high risk of developing breast and ovarian cancer. Breast conserving therapy is associated with a similar risk of ipsilateral cancer recurrence in BRCA carriers compared with non-carriers. However, the risk of subsequent contralateral breast cancer in carriers is markedly increased. Therefore, mastectomy of the diseased breast along with risk reducing mastectomy of the contralateral breast is often advocated for BRCA carriers who are treated for early breast cancer. Yet, many BRCA carriers forgo this option for fear of harmful effects and choose breast conserving treatment and observation instead. In Israel, BRCA-associated breast cancer is relatively common. Accordingly, a national protocol was devised for this enriched population.Patients and methodsIn this Institutional Review Board-approved phase II trial, the option of prophylactic irradiation to the contralateral breast, in addition to standard loco-regional treatment, was offered to BRCA carrier patients treated for early breast cancer who declined contralateral mastectomy. The primary end point was contralateral breast cancer.ResultsBetween May 2007 and October 2017, 162 patients were enrolled. Eighty-one patients opted for standard loco-regional treatment including surgery and radiation to the involved side (control arm) and 81 patients chose additional contralateral breast irradiation (intervention arm). At a median follow-up of 58 months, 10 patients developed contralateral breast cancer in the control arm at a median of 32 months, as compared with 2 patients in the intervention arm who developed contralateral breast cancer 80 and 105 months after bilateral breast irradiation (log-rank P = 0.011).ConclusionsAmong BRCA carrier patients treated for early breast cancer, the addition of contralateral breast irradiation was associated with a significant reduction of subsequent contralateral breast cancers and a delay in their onset.Clinical trialPhase II, comparative two-arm trial (NCT00496288).     

Changes in breast cancer risk associated with different volumes,doses, and techniques in female Hodgkin lymphoma patients treated with supra-diaphragmatic radiation therapy

PurposeThe contribution of thoracic radiation in increasing secondary breast cancer (BC) risk in female Hodgkin lymphoma patients is well known, and recent changes in radiation therapy volumes, doses and techniques are supposed to minimize it. In this study, we compared different radiation therapy solutions in terms of secondary BC induction risk with the aim of selecting which could be considered the most protective.Methods and MaterialsIn 10 female patients under 30 years old we estimated breast cancer risk for different combined treatment solutions (involved field vs involved nodal radiation therapy [IFRT vs INRT], 30 Gy vs 20 Gy, 3-dimensional conformal radiation therapy vs volumetric modulated arc therapy [3DCRT vs VMAT]). The organ equivalent dose (OED) method was used for dose calculation, as OED is directly related to the excess risk. Estimated OED mean values for all options in all patients were then analyzed and compared.ResultsINRT was significantly associated with a lower OED, regardless of total dose and technique (0.43 vs 1.15, P < .0001). The relative OED reduction from IFRT to INRT was approximately 60%. The dose of 20 Gy resulted in a significant reduction of OED, approximately 25% (0.68 vs 0.9, P < .01). VMAT did not show significantly higher OED when compared with 3DCRT (0.84 vs 0.74, P = .15). The combination of INRT and 20 Gy lead to a decrease in OED of approximately 70% if compared with IFRT 30 Gy.ConclusionsThe INRT approach substantially reduces OED, independent of dose and technique; the dose reduction from 30 Gy to 20 Gy also has a significant impact, and as expected INRT-20 Gy resulted to be the solution at lowest risk. No differences were observed when comparing different techniques (3DCRT vs VMAT). The combination of these innovative approaches might lead to a substantial reduction in secondary breast cancer risk in this patient population.     

Identification of women with an increased risk of developing radiation-induced breast cancer

In the previous issue of Breast Cancer Research, Broeks and collaborators present the results of a study suggesting that germline mutations in BRCA1, BRCA2, ATM or CHEK2 may double the risk of radiation-induced contralateral breast cancer following radiotherapy for a first breast cancer. The assocation appeared to be strongest among women who were below the age of 40 at the time of their first breast cancer and among women who developed their second cancer 5 years or more after the first. While there were a number of methodological issues that might limit the conclusions drawn from this paper, this is one of several recent studies suggesting that carriers of pathogenic alleles in DNA repair and damage recognition genes may have an increased risk of breast cancer following exposure to ionising radiation, even at low doses. This finding has important implications for the protection of breast cancer patients and their close relatives. If confirmed, mutation carriers may wish to consider alternatives to X-ray for diagnostic purposes. The need for tailored cancer treatment strategies in carriers should also be evaluated carefully.     

Mammographic screening in BRCA1 mutation carriers postponed until age 40: Evaluation of benefits,costs and radiation risks using models

PurposeBRCA1 mutation carriers are offered screening with magnetic resonance imaging (MRI) and mammography. The aim of this study was to weigh benefits and risks of postponing mammographic screening until age 40.MethodsWith the MISCAN microsimulation model two screening protocols were evaluated: 1) the current Dutch guidelines: annual MRI from age 25–60, annual mammography from age 30–60, and biennial mammography in the nationwide program from age 60–74, and 2) the modified protocol: with annual mammography postponed until age 40. A cost-effectiveness analysis was performed.The risks of radiation-induced breast cancer mortality were estimated with absolute and relative exposure-risk models of the 7th Biological Effects of Ionising Radiation Committee.ResultsCurrent screening guidelines prevent 13,139 breast cancer deaths per 100,000 BRCA1 mutation carriers. Postponing mammography until age 40 would increase breast cancer deaths by 23 (0.17%), but would also reduce radiation-induced breast cancer deaths by 15 or 105 using the absolute and relative risk model respectively per 100,000 women screened. The estimated net effect is an increase of eight or a reduction of 82 breast cancer deaths per 100,000 women screened (depending on the risk model used). The incremental cost of mammograms between age 30–39 is €272,900 per life year gained.ConclusionsThe modified protocol may be slightly less effective or even better than the current guidelines. The high cost-savings justify a possible small loss of effectiveness.     

Breast conserving surgery in locoregional treatment of breast carcinoma after Hodgkin lymphoma

PurposeTo report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery.Patients and methodsMedical records of 72 women who developed either ductal carcinoma in situ or stage I–III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed.ResultsMedian age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%).ConclusionsBreast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position.     

Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment

Summary Background. To quantify the risk of soft tissue and bone sarcomas after breast cancer according to the doses and technical modalities of irradiation.Methods. We followed a cohort of 6597 breast-cancer patients for 8.3 years on average. The number of soft tissue and bone sarcomas was compared to the expected number based on the incidence rates in the general French population. We also estimated the risk of sarcoma according to the radiation dose received at site of the sarcoma in a nested case control study of 14 breast-cancer patients who subsequently developed a sarcoma and 98 controls matched for age at diagnosis of breast cancer, period of initial treatment and length of follow-up.Results. In the cohort-study, 12 women who had initially received radiotherapy treatment developed a bone or soft tissue sarcoma during the follow-up period. The expected number of cases during this period was 1.7 (SIR=7.0, 95% CI: 3.7–11.7) and the mean annual excess incidence during the same period was 21 per 100,000 person-years. The 15-year cumulative incidence of sarcoma was 0.28% (95% CI: 0.10–0.45%). In the case–control study, all the 14 cases had received at least 11.8 Gray at the site of the sarcoma, which was always located in the irradiated field or in the upper ipsilateral extremity of the arm. A dose–effect relationship was observed (p < 0.001). The best fit was obtained for a quadratic dose–response relationship, without a negative exponential term for cell killing at high doses. The risk of sarcoma was 30.6 higher for doses of more than 44 Gray than for doses of less than 15 Gray.Conclusions. High doses of radiation strongly increase the risk of bone and soft tissue sarcoma.     

Contralateral breast cancers following treatment for initial breast cancers in women

The risk of a second primary cancer arising in the contralateral breast following treatment of an initial breast cancer was evaluated for 1,630 women whose first breast cancers were diagnosed and treated at University of California at Los Angeles between 1955 and 1979. Based on follow-up data ranging from 5 to 30 years, the rate of development of nonsimultaneous contralateral breast cancers was slightly in excess of 2.5 per 1,000 person-years at risk. There was no detectably significant difference in the frequency of second primary cancers related to the type of treatment of the first cancers, whether that was surgery, radiation therapy, or surgery plus radiation therapy.     

Model-Based Selection for Proton Therapy in Breast Cancer: Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences

AimsProton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences.Materials and methodsA national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy.ResultsThe model of Darby et al. (N Engl J Med 2013; 368:987–82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021.ConclusionThe NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands.     

Dose- and time-response for breast cancer risk after radiation therapy for benign breast disease.

Exposure of the breast to ionising radiation increases the risk of breast cancer, especially among young women. However, some issues remain controversial, for instance the shape of the dose-response curve and the expression of time-related excess. The main purpose of this report was to examine the dose-response curves for radiation-induced breast cancer formulated according to radiobiological target theories. Another purpose was to analyse the time-related excess of breast cancer risk after exposure when dose and age at first exposure were held constant. Breast cancer incidence was analysed in a cohort of 3090 women diagnosed with benign breast disease during 1925-61 (median age 37 years). Of these, 1216 were treated with radiation therapy. The dose range was 0-50 Gy (mean 5.8 Gy). The incidence rate as function of dose was analysed using a linear-quadratic Poisson regression model. Cell-killing effects and other modifying effects were incorporated through additional log-linear terms. Additive and multiplicative models were compared in estimating the time-related excess. The analysis, which was based on 278 breast cancer cases, showed a linear dose-response relationship at low to medium dose levels with a cell-killing effect of 5% Gy-1 (95% confidence interval 2-9%). For a given absorbed dose and age at first exposure the time-related excess was proportional to the background rates with a suggestion that the excess remains throughout life.     

Second solid cancers after radiotherapy for breast cancer in SEER cancer registries

Background:

Radiotherapy for breast cancer reduces disease recurrence and breast cancer mortality. However, it has also been associated with increased second cancer risks in exposed sites.

Methods:

We evaluated long-term second cancer risks among 182 057 5-year survivors of locoregional invasive breast cancer diagnosed between 1973 and 2000 and reported to US NCI-SEER Program cancer registries. Multivariate Poisson regression was used to estimate the relative risk (RR) and excess cases of second cancer in women who had surgery and radiotherapy, compared with those who had surgery alone. Second cancer sites were grouped according to doses received from typical tangential breast fields.

Results:

By the end of 2005 (median follow-up=13.0 years), 15 498 second solid cancers had occurred, including 6491 contralateral breast cancers. The RRs for radiotherapy were 1.45 (95% confidence interval (CI)=1.33–1.58) for high-dose second cancer sites (1+ Gy: lung, oesophagus, pleura, bone and soft tissue) and 1.09 (1.04–1.15) for contralateral breast cancer (≈1 Gy). These risks decreased with increasing age and year of treatment. There was no evidence of elevated risks for sites receiving medium (0.5–0.99 Gy, RR=0.89 (0.74–1.06)) or low doses (<0.5 Gy, RR=1.01 (0.95–1.07)). The estimated excess cases of cancer in women treated with radiotherapy were as follows: 176 (95% CI=69–284) contralateral breast cancers or 5% (2–8%) of the total in all 1+year survivors, and 292 (222–362) other solid cancers or 6% (4–7%) of the total.

Conclusions:

Most second solid cancers in breast cancer survivors are not related to radiotherapy.     

Leukemia risk following radiotherapy for breast cancer

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.     

Population-based mammography screening below age 50: balancing radiation-induced vs prevented breast cancer deaths

Introduction:

Exposure to ionizing radiation at mammography screening may cause breast cancer. Because the radiation risk increases with lower exposure age, advancing the lower age limit may affect the balance between screening benefits and risks. The present study explores the benefit–risk ratio of screening before age 50.

Methods:

The benefits of biennial mammography screening, starting at various ages between 40 and 50, and continuing up to age 74 were examined using micro-simulation. In contrast with previous studies that commonly used excess relative risk models, we assessed the radiation risks using the latest BEIR-VII excess absolute rate exposure-risk model.

Results:

The estimated radiation risk is lower than previously assessed. At a mean glandular dose of 1.3 mGy per view that was recently measured in the Netherlands, biennial mammography screening between age 50 and 74 was predicted to induce 1.6 breast cancer deaths per 100 000 women aged 0–100 (range 1.3–6.3 extra deaths at a glandular dose of 1–5 mGy per view), against 1121 avoided deaths in this population. Advancing the lower age limit for screening to include women aged 40–74 was predicted to induce 3.7 breast cancer deaths per 100 000 women aged 0–100 (range 2.9–14.4) at biennial screening, but would also prevent 1302 deaths.

Conclusion:

The benefits of mammography screening between age 40 and 74 were predicted to outweigh the radiation risks.     

Unilateral and bilateral breast cancer in women surviving pediatric Hodgkin's disease

PURPOSE: To define demographic and therapeutic associations with the risk of breast cancer in children treated for Hodgkin's disease (HD), particularly the frequency and interval to the development of contralateral breast cancer. METHODS AND MATERIALS: All 398 female patients (<19 years) treated for HD in five institutions during the accrual period were evaluated. Mean follow-up was 16.9 years. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cases to the expected number of cases, estimated using age-matched controls from the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 29 women developed breast cancer (25 invasive, 4 ductal carcinoma in situ; SIR, 37.25; 95% confidence interval, 24.96-53.64). Time to diagnosis was 9.4 to 36.1 years. Cumulative incidence was 24% at 30 years. Ten patients (34%) had bilateral disease (9 metachronous, 1 synchronous). The interval to contralateral breast cancer was 12 to 34 months. On univariate analysis, significant variables included stage of HD, mantle radiation dose, pelvic radiation (protective), and follow-up time. On multivariate analysis, early stage and older age at diagnosis of HD (12 years) were significant predictors of secondary breast cancer. CONCLUSIONS: Women surviving pediatric HD were found to have a 37-fold increase in the risk of breast cancer and a high likelihood of rapidly developing bilateral disease. Early-stage HD and age greater than 12 years at diagnosis of HD were independent risk factors. Higher radiation doses may augment risk, and pelvic radiation may be protective. Breast cancer screening methodology and frequency, plus the role of prophylaxis in patients with unilateral disease, require definition.     

Cardiovascular effects of breast cancer radiotherapy

Cardiac toxicity has been implicated as the primary reason for excess non-breast cancer mortality in early breast cancer radiotherapy studies. Refinements in radiotherapy techniques have allowed for a considerable reduction of this risk in the majority of breast cancer patients. Recent large population-based studies confirmed an increase of cardiovascular death risk in patients irradiated for cancer of the left breast and in individuals exposed to relatively low (hitherto believed to be of no cardiovascular disease risk) doses of radiation, such as atomic bomb survivors or patients treated for various benign conditions. The issue of potential radiation-related cardiac damage may also be assuming a new significance due to the widespread use of other cardiotoxic agents, such as anthracyclines, paclitaxel and trastuzumab. The aim of this review is to summarize and critically analyze the available evidence on the impact of ionizing radiation on the cardiovascular system, with special attention to recent data demonstrating previously unrecognized adverse effects. This review discusses the pathology of radiation-related cardiovascular disease, its clinical presentation, risk factors and methods of assessment, as well as technical developments minimizing cardiac exposure. Epidemiological data are presented on the incidence of radiation-induced heart disease and cardiovascular mortality in various populations of patients irradiated for breast cancer and in individuals exposed to low radiation doses. Additionally, non-cardiac radiation-related vascular morbidity and mortality in breast cancer patients are addressed.     

Outcome After Breast Conservation Treatment with Radiation for Women with Triple-Negative Early-Stage Invasive Breast Carcinoma

BackgroundTriple-negative breast carcinoma is defined by a primary tumor that is estrogen receptor negative, progesterone receptor negative, and HER2 negative. The current study was performed to determine the relationship of triple-negative tumor status to outcome after breast conservation treatment with radiation.Patients and MethodsA total of 519 women with early-stage invasive breast carcinoma underwent breast conservation treatment with radiation. Of the 519 primary breast carcinomas, 90 (17%) were triple negative and 429 (83%) were not triple negative. The median follow-up after treatment was 3.9 years.ResultsCompared with the patients without a triple-negative tumor, the patients with a triple-negative tumor had a higher 8-year rate of any local failure (8% vs. 4%, respectively; P = .041) and a lower 8-year rate of freedom from distant metastases (81% vs. 92%, respectively; P = .0066). There were no differences between the 2 groups for local-only first failure, overall survival, or contralateral breast cancer (all P ≥ .3). On multivariate analysis, triple-negative tumors had an increased risk for any local failure (hazard ratio, 2.58), although this difference was not statistically significant (P = .097).ConclusionAfter breast conservation treatment with radiation, women with a triple-negative tumor had a higher rate of local failure compared with women without a triple-negative tumor. However, the absolute difference in local failure between the 2 groups was relatively small and therefore does not preclude breast conservation treatment with radiation for triple-negative early-stage invasive breast carcinoma.     

早期乳腺癌保乳术后调强放疗

现行早期乳腺癌保乳术后的常规切线野放射治疗技术存在靶区内剂量不均匀的缺陷.国内外多位研究者将调强放疗(IMRT)应用于保乳术后患者,以期在提高靶区剂量均匀性、降低危及器官受量及改善美容效果方面体现出一定优势.     

Malignant breast tumors after radiotherapy for a first cancer during childhood.

PURPOSE: To assess the specific role of treatment and type of first cancer (FC) in the risk of long-term subsequent breast cancer (BC) among childhood cancer survivors. PATIENTS AND METHODS: In a cohort of 1,814 3-year female survivors treated between 1946 and 1986 in eight French and English centers, data on chemotherapy and radiotherapy were collected. Individual estimation of radiation dose to each breast was performed for the 1,258 patients treated by external radiotherapy; mean dose to breast was 5.06 Gy (range, 0.0 to 88.0 Gy) delivered in 20 fractions (mean). RESULTS: Mean follow-up was 16 years; 16 patients developed a clinical BC, 13 after radiotherapy. The cumulative incidence of BC was 2.8% (95% CI, 1.0% to 4.5%) 30 years after the FC and 5.1% (95% CI, 2.1% to 8.2%) at the age of 40 years. The annual excess incidence increased as age increased, whereas the standardized incidence ratio decreased. On average, each Gray unit received by any breast increased the excess relative risk of BC by 0.13 (< 0.0 to 0.75). After stratification on castration and attained age, and adjusting for radiation dose, FC type, and chemotherapy, a higher risk of a subsequent BC was associated with Hodgkin's disease (relative risk, 7.0; 95% CI, 1.4 to 30.9). CONCLUSION: The reported high risk of BC after childhood Hodgkin's disease treatment seems to be due not only to a higher radiation dose to the breasts, but also to a specific susceptibility.