Correlation of High-Sensitivity Cardiac Troponin I Values and Cardiac Radiation Doses in Patients with Left-Sided Breast Cancer Undergoing Hypofractionated Adjuvant Radiotherapy with Concurrent Anti-HER2 Therapy.

Anti HER2 therapy and left breast adjuvant radiation therapy (RT) can both result in cardiotoxicity. The aim of this study was to evaluate the influence of radiation dose on cardiac structures on the values of the early cardiotoxicity marker high-sensitivity cardiac troponin I (hscTnI) in patients with HER2-positive left breast cancer undergoing adjuvant concomitant antiHER2 therapy and radiotherapy, and to establish a correlation between the hscTnI values and cardiac radiation doses. Sixty-one patients underwent left breast hypofractionated radiotherapy in parallel with anti-HER2 therapy: trastuzumab, combined trastuzumab-pertuzumab or trastuzumab emtansine (T-DM1). The hscTnI values were measured prior to and upon completion of radiotherapy. A significant increase in hscTnI was defined as >30% from baseline, with the second value being 4 ng/L or higher. Dose volume histograms (DVH) were generated for the heart, left ventricle (LV) and left anterior descending artery (LAD). The hscTnI levels were corelated with radiation doses on cardiac structures. An increase in hscTnI values was observed in 17 patients (Group 1). These patients had significantly higher mean radiation doses for the heart (p = 0.02), LV (p = 0.03) and LAD (p = 0.04), and AUC for heart and LV (p = 0.01), than patients without hscTnI increase (Group 2). The patients in Group 1 also had larger volumes of heart and LV receiving 2 Gy (p = 0.01 for both) and 4 Gy (p = 0.02 for both). LAD differences were observed in volumes receiving 2 Gy (p = 0.03), 4 Gy (p = 0.02) and 5 Gy (p = 0.02). The increase in hscTnI observed in patients receiving anti-HER2 therapy after adjuvant RT was positively associated with radiation doses on the heart, LV and LAD.

Complication Rates in Therapeutic Versus Prophylactic Bilateral Mastectomies: Insights From a National Database.

BACKGROUND: The "Jolie effect" and other media focus on prophylactic treatments have resulted in unilateral breast cancer patients increasingly undergoing contralateral prophylactic mastectomy. Little is known, however, regarding outcomes following therapeutic versus prophylactic mastectomy. In this study, we compared complication rates of unilateral breast cancer patients undergoing contralateral prophylactic mastectomy (BM-TP) to patients undergoing bilateral prophylactic mastectomy (BM-P). METHODS: The BM-TP and BM-P patients from 2015 to 2019 were identified in Optum Clinformatics DataMart. Six-month outcomes were assessed and included wound complications, infection, hematoma/seroma, breast pain, fat necrosis, flap failure, implant failure/removal, other flap/implant complications, and other complications. Multivariable regression models adjusted for age, residence, insurance, race, and Charlson Comorbidity Index score. RESULTS: Of 9319 women, 7114 (76.3%) underwent BM-TP, and 2205 (23.7%) underwent BM-P. In multivariable analysis, BM-TP had higher odds of overall complications (adjusted odds ratio [aOR], 1.35; P < 0.0001), but no difference was observed among patients who had autologous ( P = 0.1448) or no breast reconstruction ( P = 0.1530). Higher odds of overall complications persisted even after controlling for radiation therapy (aOR, 1.25; P = 0.0048) and chemotherapy (aOR, 1.28; P = 0.0047), but not after controlling for lymph node surgery ( P = 0.7765). CONCLUSION: The BM-TP (vs BM-P) patients face higher odds of overall complications but without any difference in certain reconstructive modalities or after controlling for lymph node surgery.

Recent Postoperative Radiotherapy for Left-sided Breast Cancer Does Not Increase Mortality of Heart Disease in Asians or Pacific Islanders: SEER Database Analysis.

BACKGROUND/AIM: The purpose of this study was to evaluate the impact of recent radiotherapy on mortality from heart disease in Asians or Pacific islanders with breast cancer using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: Asians or Pacific islanders with stage 0 or I (AJCC 6th) breast cancer between 2000 and 2015 were analyzed. The impact of radiotherapy for mortality from heart disease after treatment was evaluated by comparing patients who received radiotherapy for left-sided breast cancer, patients who received radiotherapy for right-sided breast cancer and patients who did not receive radiotherapy. RESULTS: In 25,684 Asians or Pacific islanders, the incidence of cardiac death was higher in patients who did not receive radiotherapy than in patients who received radiotherapy. Among patients who received external beam irradiation, the incidence of cardiac death was 2.00% for patients with left-sided breast cancer and 1.69% for patients with right-sided breast cancer, with no significant difference (chi-square test, p=0.427). In the period from 2000 to 2008, there was no significant difference between the cumulative heart-related death rates in patients who received radiotherapy and in patients who did not receive radiotherapy (Tarone-Ware test, p=0.406); however, in 2009-2015, the cumulative heart-related death rate in patients who did not receive radiotherapy was significantly higher than that in patients who received radiotherapy (log-rank test, p<0.001). CONCLUSION: Heart-related death after treatment for breast cancer is relatively rare in Asians or Pacific islanders. Since at least 2000, the cardiac impact of postoperative radiotherapy has not been significant.

Risk factors of unilateral breast cancer-related lymphedema: an updated systematic review and meta-analysis of 84 cohort studies.

PURPOSE: To review and update the incidence and risk factors for breast cancer-related lymphedema based on cohort studies. METHODS: The study was guided by the Joanna Briggs Institute methodology and the Cochrane handbook for systematic reviews. PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, CNKI, SinoMed, and Wan Fang Database were searched from inception to November 15, 2021. Cohort studies reported adjusted risk factors were selected. PRISMA guideline was followed. Study quality were evaluated using the Newcastle-Ottawa scale. Random-effects models were adopted. The robustness of pooled estimates was validated by meta-regression and subgroup analysis. Lymphedema incidence and adjusted risk factors in the multivariable analyses with hazard / odds ratios and 95% CIs were recorded. RESULTS: Eighty-four cohort studies involving 58,358 breast cancer patients were included. The pooled incidence of lymphedema was 21.9% (95% CI, 19.8-24.0%). Fourteen factors were identified including ethnicity (black vs. white), higher body mass index, higher weight increase, hypertension, higher cancer stage (III vs. I-II), larger tumor size, mastectomy (vs. breast conservation surgery), axillary lymph nodes dissection, more lymph nodes dissected, higher level of lymph nodes dissection, chemotherapy, radiotherapy, surgery complications, and higher relative volume increase postoperatively. Additionally, breast reconstruction surgery, and adequate finance were found to play a protective role. However, other variables such as age, number of positive lymph nodes, and exercise were not correlated with risk of lymphedema. CONCLUSION: Treatment-related factors still leading the development of breast cancer-related lymphedema. Other factors such as postoperative weight increase and finance status also play a part. Our findings suggest the need to shift the focus from treatment-related factors to modifiable psycho-social-behavioral factors.

Risk of coronary stenosis after adjuvant radiotherapy for breast cancer.

PURPOSE: Adjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT. METHODS: A cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence. RESULTS: A total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21-1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22-2.10), 1.38 (95% CI 1.07-1.78), and 2.43 (95% CI 1.33-4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT. CONCLUSION: Implementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.

Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy.

BACKGROUND: To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). PATIENTS AND METHODS: We enrolled 646 women with left-breast IDC at clinical stages I-IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs). RESULTS: In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37-0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79-0.96; P = 0.0356) and 0.89 (0.54-1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group. CONCLUSION: Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.

Dosimetric evaluation of deep inspiration breath hold for left-sided breast cancer: analysis of patient-specific parameters related to heart dose reduction.

Deep inspiration breath hold (DIBH) is a common method used worldwide for reducing the radiation dose to the heart. However, few studies have reported on the relationship between dose reduction and patient-specific parameters. The aim of this study was to compare the reductions of heart dose and volume using DIBH with the dose/volume of free breathing (FB) for patients with left-sided breast cancer and to analyse patient-specific dose reduction parameters. A total of 85 Asian patients who underwent whole-breast radiotherapy after breast-conserving surgery were recruited. Treatment plans for FB and DIBH were retrospectively generated by using an automated breast planning tool with a two-field tangential intensity-modulated radiation therapy technique. The prescribed dose was 50 Gy in 25 fractions. The dosimetric parameters (e.g., mean dose and maximum dose) in heart and lung were extracted from the dose-volume histogram. The relationships between dose-volume data and patient-specific parameters, such as age, body mass index (BMI), and inspiratory volume, were analyzed. The mean heart doses for the FB and DIBH plans were 1.56 Gy and 0.75 Gy, respectively, a relative reduction of 47%. There were significant differences in all heart dosimetric parameters (p < 0.001). For patients with a high heart dose in the FB plan, a relative reduction of the mean heart dose correlated with inspiratory volume (r = 0.646). There was correlation between the relative reduction of mean heart dose and BMI (r = -0.248). We recommend considering the possible feasibility of DIBH in low BMI patients because the degree of benefit from DIBH varied with BMI.

Radiation dose and cardiac risk in breast cancer treatment: An analysis of modern radiation therapy including community settings.

PURPOSE: Adjuvant radiation therapy (RT) for breast cancer improves outcomes, but prior studies have documented substantive cardiac dose and cardiac risk. We assessed the mean heart dose (MHD) of RT and estimated the risk of RT-associated cardiac toxicity in women undergoing adjuvant RT for breast cancer in contemporary (predominantly) community practice. METHODS AND MATERIALS: We identified women with left-sided breast cancer receiving adjuvant RT between 2012 and 2014 from 94 centers across 16 states. We used bivariate analyses and multivariable linear regression to assess associations between RT techniques and MHD. Excess RT-related cardiac risk by age 80 was estimated for women diagnosed at age 60 using the previously reported relationship between MHD and cardiac risk. RESULTS: Among 1161 women, 77.3% were treated in community practice and with breast conservation (77.8%). The most common techniques were free-breathing (92.2%), supine (94.8%), and fixed gantry intensity modulated RT (FG-IMRT; 46.9%). The median MHD was 2.76 Gy (interquartile range, 1.47-5.03). In multivariable analyses, the predicted median MHD with deep inspiration breath hold was 2.41 Gy compared with 3.86 Gy with free-breathing (P < .001). Three-dimensional conformal RT (3D-CRT) was associated with a lower predicted median MHD (2.78 Gy) than FG-IMRT (4.02 Gy) or rotational IMRT, 6.60 Gy, P < .001). For 60-year-old women with the median MHD of the study population (2.76 Gy) and no cardiovascular risk factors, the 20-year predicted excess risk of death from ischemic heart disease attributable to radiation was 3.5 excess events/1000 patients, in contrast to estimates of 8 events/1000 from prior analyses. The predicted risk of cardiac events varied based on radiation technique, with 4 excess events/1000 with 3D-CRT, 5 excess events/1000 with FG-IMRT, and 8 excess events/1000 with rotational IMRT. CONCLUSIONS: MHD varies substantially across patients and is influenced by technique in predominantly community settings. Overall risk of cardiac toxicity is modest.

Second Cancer Risk after simultaneous integrated boost radiation therapy of right sided breast cancer with and without flattening filter.

BACKGROUND: The aim of this study was to investigate if the flattening filter free mode (FFF) of a linear accelerator reduces the excess absolute risk (EAR) for second cancer as compared to the flat beam mode (FF) in simultaneous integrated boost (SIB) radiation therapy of right-sided breast cancer. PATIENTS AND METHODS: Six plans were generated treating the whole breast to 50.4 Gy and a SIB volume to 63 Gy on CT data of 10 patients: intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and a tangential arc VMAT (tVMAT), each with flattening filter and without. The EAR was calculated for the contralateral breast and the lungs from dose-volume histograms (DVH) based on the linear-exponential, the plateau, and the full mechanistic dose-response model. Peripheral low-dose measurements were performed to compare the EAR in more distant regions as the thyroids and the uterus. RESULTS: FFF reduces the EAR significantly in the contralateral and peripheral organs for tVMAT and in the peripheral organs for VMAT. No reduction was found for IMRT. The lowest EAR for the contralateral breast and lung was achieved with tVMAT FFF, reducing the EAR by 25 % and 29 % as compared to tVMAT FF, and by 44 % to 58 % as compared to VMAT and IMRT in both irradiation modes. tVMAT FFF showed also the lowest peripheral dose corresponding to the lowest EAR in the thyroids and the uterus. CONCLUSION: The use of FFF mode allows reducing the EAR significantly when tVMAT is used as the treatment technique. When second cancer risk is a major concern, tVMAT FFF is considered the preferred treatment option in SIB irradiation of right-sided breast cancer.

Modern Radiation Therapy and Cardiac Outcomes in Breast Cancer.

PURPOSE: Adjuvant radiation therapy, which has proven benefit against breast cancer, has historically been associated with an increased incidence of ischemic heart disease. Modern techniques have reduced this risk, but a detailed evaluation has not recently been conducted. The present study evaluated the effect of current radiation practices on ischemia-related cardiac events and procedures in a population-based study of older women with nonmetastatic breast cancer. METHODS AND MATERIALS: A total of 29,102 patients diagnosed from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Medicare claims were used to identify the radiation therapy and cardiac outcomes. Competing risk models were used to assess the effect of radiation on these outcomes. RESULTS: Patients with left-sided breast cancer had a small increase in their risk of percutaneous coronary intervention (PCI) after radiation therapy-the 10-year cumulative incidence for these patients was 5.5% (95% confidence interval [CI] 4.9%-6.2%) and 4.5% (95% CI 4.0%-5.0%) for right-sided patients. This risk was limited to women with previous cardiac disease. For patients who underwent PCI, those with left-sided breast cancer had a significantly increased risk of cardiac mortality with a subdistribution hazard ratio of 2.02 (95% CI 1.23-3.34). No other outcome, including cardiac mortality for the entire cohort, showed a significant relationship with tumor laterality. CONCLUSIONS: For women with a history of cardiac disease, those with left-sided breast cancer who underwent radiation therapy had increased rates of PCI and a survival decrement if treated with PCI. The results of the present study could help cardiologists and radiation oncologists better stratify patients who need more aggressive cardioprotective techniques.