Identification of a novel cancer microbiome signature for predicting prognosis of human breast cancer patients

BackgroundPrognosis of breast cancer (BC) patients differs considerably and identifying reliable prognostic biomarker(s) is imperative. With evidence that the microbiome plays a critical role in the response to cancer therapies, we aimed to identify a cancer microbiome signature for predicting the prognosis of BC patients.MethodsThe TCGA BC microbiome data (TCGA-BRCA-microbiome) was downloaded from cBioPortal. Univariate and multivariate Cox regression analyses were used to examine association of microbial abundance with overall survival (OS) and to identify a microbial signature for creating a prognostic scoring model. The performance of the scoring model was assessed by the area under the ROC curve (AUC). Nomograms using the microbial signature, clinical factors, and molecular subtypes were established to predict OS and progression-free survival (PFS).ResultsAmong 1406 genera, the abundances of 94 genera were significantly associated with BC patient OS in TCGA-BRCA-microbiome dataset. From that set we identified a 15-microbe prognostic signature and developed a 15-microbial abundance prognostic scoring (MAPS) model. Patients in low-risk group significantly prolong OS and PFS as compared to those in high-risk group. The time-dependent ROC curves with MAPS showed good predictive efficacy both in OS and PFS. Moreover, MAPS is an independent prognostic factor for OS and PFS over clinical factors and PAM50-based molecular subtypes and superior to the previously published 12-gene signature. The integration of MAPS into nomograms significantly improved prognosis prediction.ConclusionMAPS was successfully established to have independent prognostic value, and our study provides a new avenue for developing prognostic biomarkers by microbiome profiling.

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.

Long-term results of a randomized partial irradiation trial compared to whole breast irradiation in the early stage and low-risk breast cancer patients after conservative surgery

Purpose To report long-term results of a randomized trial comparing accelerated partial breast irradiation (APBI) to whole-breast irradiation (WBI) in terms of efficacy, toxicity, and cosmesis. Methods and materials WBI group was treated with 3D conformal external irradiation, 2 Gy daily/fraction, 5 fractions/week, to a total dose of 50 Gy. APBI group was treated with 3D conformal external irradiation 3.75 Gy/fraction, twice a day, 5 fractions/week, to a total dose of 37.5 Gy in the APBI group. Patients were followed up every 6 months up to 5 years and yearly thereafter. During follow-up visits, the clinician evaluated chronic toxicity and scored cosmetic results with a four-scale system. Results After a median follow-up of 10.3 years, 43 patients in each group (84%) are alive without disease. One patient died after disease progression in the APBI arm, and there was no death in the WBI arm. The rest of the patients died from another disease different than breast cancer, similarly between groups. There was greater fibrosis in the APBI group (9 patients grade 1 and one grade 2) compared to WBI (3 patients grade 1 and one grade 2); p = 0.18. Regarding cosmesis, in APBI group, 19 and 21 (43.2 and 47%) patients had excellent or good results, similar to the WBI group with 18 patients (40.9%) in each cosmesis outcome. The WBI group did not have any patient with poor cosmesis but the APBI had 3 (6.8%; p = 0.24). Conclusion After a follow-up of 10 years, there were no differences in efficacy between the 2 treatment arms. Despite slight greater toxicity in the APBI group, the cosmesis was similar and satisfactory in both groups (AU)

Long-term results of a randomized partial irradiation trial compared to whole breast irradiation in the early stage and low-risk breast cancer patients after conservative surgery.

PURPOSE: To report long-term results of a randomized trial comparing accelerated partial breast irradiation (APBI) to whole-breast irradiation (WBI) in terms of efficacy, toxicity, and cosmesis. METHODS AND MATERIALS: WBI group was treated with 3D conformal external irradiation, 2 Gy daily/fraction, 5 fractions/week, to a total dose of 50 Gy. APBI group was treated with 3D conformal external irradiation 3.75 Gy/fraction, twice a day, 5 fractions/week, to a total dose of 37.5 Gy in the APBI group. Patients were followed up every 6 months up to 5 years and yearly thereafter. During follow-up visits, the clinician evaluated chronic toxicity and scored cosmetic results with a four-scale system. RESULTS: After a median follow-up of 10.3 years, 43 patients in each group (84%) are alive without disease. One patient died after disease progression in the APBI arm, and there was no death in the WBI arm. The rest of the patients died from another disease different than breast cancer, similarly between groups. There was greater fibrosis in the APBI group (9 patients grade 1 and one grade 2) compared to WBI (3 patients grade 1 and one grade 2); p = 0.18. Regarding cosmesis, in APBI group, 19 and 21 (43.2 and 47%) patients had excellent or good results, similar to the WBI group with 18 patients (40.9%) in each cosmesis outcome. The WBI group did not have any patient with poor cosmesis but the APBI had 3 (6.8%; p = 0.24). CONCLUSION: After a follow-up of 10 years, there were no differences in efficacy between the 2 treatment arms. Despite slight greater toxicity in the APBI group, the cosmesis was similar and satisfactory in both groups.

Effects of deep inspiration breath hold on prone photon or proton irradiation of breast and regional lymph nodes.

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments.

Validity of the prognostication tool PREDICT version 2.2 in Japanese breast cancer patients.

INTRODUCTION: PREDICT is a prognostication tool that calculates the potential benefit of various postsurgical treatments on the overall survival (OS) of patients with nonmetastatic invasive breast cancer. Once patient, tumor, and treatment details have been entered, the tool will show the estimated 5-, 10-, and 15-year OS outcomes, both with and without adjuvant therapies. This study aimed to conduct an external validation of the prognostication tool PREDICT version 2.2 by evaluating its predictive accuracy of the 5- and 10-year OS outcomes among female patients with nonmetastatic invasive breast cancer in Japan. METHODS: All female patients diagnosed from 2001 to 2013 with unilateral, nonmetastatic, invasive breast cancer and had undergone surgical treatment at Kyushu University Hospital, Fukuoka, Japan, were selected. Observed and predicted 5- and 10-year OS rates were analyzed for the validation population and the subgroups. Calibration and discriminatory accuracy were assessed using Chi-squared goodness-of-fit test and area under the receiver operating characteristic curve (AUC). RESULTS: A total of 636 eligible cases were selected from 1, 213 records. Predicted and observed OS differed by 0.9% (p = 0.322) for 5-year OS, and 2.4% (p = 0.086) for 10-year OS. Discriminatory accuracy results for 5-year (AUC = 0.707) and 10-year (AUC = 0.707) OS were fairly well. CONCLUSION: PREDICT tool accurately estimated the 5- and 10-year OS in the overall Japanese study population. However, caution should be used for interpretation of the 5-year OS outcomes in patients that are ≥65 years old, and also for the 10-year OS outcomes in patients that are ≥65 years old, those with histologic grade 3 and Luminal A tumors, and in those considering ETx or no systemic treatment.

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.

Salvage Mastectomy Versus Second Conservative Treatment for Second Ipsilateral Breast Tumor Event: A Propensity Score-Matched Cohort Analysis of the GEC-ESTRO Breast Cancer Working Group Database.

PURPOSE: Second conservative treatment has emerged as an option for patients with a second ipsilateral breast tumor event after conserving surgery and breast irradiation. We aimed to address the lack of evidence regarding second breast event treatment by comparing oncologic outcomes after conservative treatment or mastectomy. METHODS AND MATERIALS: Oncologic outcomes were analyzed using a propensity score-matched cohort analysis study on patients who received a diagnosis of a second breast event between January 1995 and June 2017. Patient data were collected from 15 hospitals/cancer centers in 7 European countries. Patients were offered mastectomy or lumpectomy plus brachytherapy. Propensity scores were calculated with logistic regression and multiple imputations. Matching (1:1) was achieved using the nearest neighbor method, including 10 clinical/pathologic data related to the second breast event. The primary endpoint was 5-year overall survival from the salvage surgery date. Secondary endpoints were 5-year cumulative incidence of third breast event, regional relapse and distant metastasis, and disease-free and specific survival. Complications and 5-year incidence of mastectomy were investigated in the conservative treatment cohort. RESULTS: Among the 1327 analyzed patients (mastectomy, 945; conservative treatment, 382), 754 were matched by propensity score (mastectomy, 377; conservative treatment, 377). The median follow-up was 75.4 months (95% confidence interval [CI], 65.4-83.3) and 73.8 months (95% CI, 67.5-80.8) for mastectomy and conservative treatment, respectively (P = .9). In the matched analyses, no differences in 5-year overall survival and cumulative incidence of third breast event were noted between mastectomy and conservative treatment (88% [95% CI, 83.0-90.8] vs 87% [95% CI, 82.1-90.2], P = .6 and 2.3% [95% CI, 0.7-3.9] vs 2.8% [95% CI, 0.8-4.7], P = .4, respectively). Similarly, no differences were observed for all secondary endpoints. Five-year cumulative incidence of mastectomy was 3.1% (95% CI, 1.0-5.1). CONCLUSIONS: To our knowledge, this is the largest matched analysis of mastectomy and conservative treatment combining lumpectomy with brachytherapy for second breast events. Compared with mastectomy, conservative treatment does not appear to be associated with any differences in terms of oncologic outcome. Consequently, conservative treatment could be considered a viable option for salvage treatment.

Breast cancer mortality in synchronous bilateral breast cancer patients.

BACKGROUND: Evidence suggests that patients with synchronous bilateral breast cancer (SBBC), diagnosed within 4 months, have an inferior prognosis compared to unilateral breast cancer (UBC) patients. Using data from nationwide Danish clinical databases, this cohort study investigated whether the inferior prognosis could be explained by SBBC patients having a more aggressive disease, or whether the prognosis could be explained by the fact that they have two simultaneous cancers. METHODS: Patients were diagnosed from 1999-2015. The main outcome was excess mortality, subtracting background population mortality from observed mortality. Differences between SBBC and UBC patients were evaluated by rate ratios (RR) and estimated by Poisson regression. RESULTS: In total, 1214 SBBC and 59 177 UBC patients were included. SBBC patients had a significantly higher excess mortality than UBC patients after adjustment for age and period (RR = 1.73; 95% CI:1.44-2.08; p < 0.01) and after adjusting for characteristics of the worst tumour as traditionally done (RR = 1.31; 95% CI:1.08-1.57; p = 0.01). However, adjusting for characteristics of both tumours, using a more advanced competing risks model, no difference was observed (RR = 1.01; 95% CI:0.83-1.22; p = 0.93). CONCLUSIONS: Our study does not support that the inferior prognosis in SBBC patients is due to having more aggressive tumours per se, but rather the combined effect of having two simultaneous cancers.

[Clinical characteristics and prognosis of patients with ipsilateral breast tumor recurrence after breast conservation therapy].

Objective: To analyze the clinical features and prognosis of the ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery. Methods: From 1999 to 2013, 63 women with IBTR after breast conserving surgery were retrospectively reviewed. All patients had adequate information on tumor location both at first presentation and at recurrence, with or without regional recurrence or distant metastasis. The histologic changes between true local recurrence and elsewhere recurrence groups were compared. The local recurrence, the overall survival after IBTR (IBTR-OS), the disease-free survival after IBTR (IBTR-DFS) were also compared. Results: All patients had undergone lumpectomy, including 38 cases with additional axillary lymph node dissection and 13 cases with sentinel lymph node biopsy. There were 11.3% (7/63) cases received neoadjuvant systemic therapy, 68.3% (43/63) had adjuvant radiotherapy, 60.3% (38/63) underwent adjuvant chemotherapy and 47.6% (30/63) received hormonal therapy. Forty-five cases (71.4%) had recurrence in the same quadrant, and 18 cases (28.6%) had elsewhere recurrence. Compared with histology at presentation, 10.3% of the patients (6/58) had different ones at recurrence and 28.9% of patients (13/45) had different molecular subtypes. The conversion rate of estrogen receptor status (33.3% vs 9.5%, P=0.012) and progesterone receptor status (56.3% vs 19.0%, P=0.005) in patients with elsewhere recurrence was significantly higher than that in patients with same quadrant recurrence. Fifty-nine cases had undergone surgery after IBTR, with 48 cases of secondary breast-conserving surgery and 11 cases of salvage mastectomy. The median time to IBTR of same quadrant recurrence and elsewhere recurrence groups were 26 months and 62 months (P=0.012), respectively. There were 84.4% and 44.4% cases who had local recurrence within 5 years after breast conserving surgery, respectively. Of all cases, the overall 5-year IBTR-OS and 5-year IBTR-DFS rates were 79.4% and 60.4%, respectively. There were no significant differences in 5-year IBTR-OS (77.4% vs. 83.6%, P=0.303) or 5-year IBTR-DFS (60.0% vs. 62.8%, P=0.780) between same quadrant recurrence and elsewhere recurrence groups. Univariate analysis showed that pN0-1 (P<0.001), luminal subtype (P=0.026), adjuvant endocrine therapy (P=0.007) at first presentation, recurrent tumor < 3 cm (P=0.036) and having surgery after IBTR(P=0.002) were favorable factors of IBTR-OS. pN0-1 (P<0.001) at first presentation, recurrent tumor stage Ⅰ-Ⅱ (P<0.001) and having surgery after IBTR(P=0.001) were favorable factors of IBTR-DFS. There was no significant difference between second breast-conserving surgery and salvage mastectomy in IBTR-OS and IBTR-DFS (P>0.05). Conclusions: The IBTR after breast conserving surgery mainly occurred at the original quadrant. Second breast-conserving surgery did not affect patient's prognosis. There were significant differences in biological features between the same quadrant recurrence and elsewhere recurrence, requiring different therapeutic strategies in the future.

Risk-reducing mastectomy for the prevention of primary breast cancer.

BACKGROUND: Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010. OBJECTIVES: (i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes. SEARCH METHODS: For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English. SELECTION CRITERIA: Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer. DATA COLLECTION AND ANALYSIS: At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias. MAIN RESULTS: All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or both, reported reductions after BRRM, particularly for those women with BRCA1/2 mutations. Twenty-six CRRM studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Seven studies attempted to control for multiple differences between intervention groups and showed no overall survival advantage for CRRM. Another study showed significantly improved survival following CRRM, but after adjusting for bilateral risk-reducing salpingo-oophorectomy (BRRSO), the CRRM effect on all-cause mortality was no longer significant.Twenty studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have RRM but greater variation in satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BRRM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BRRM, but there was diminished satisfaction with body image and sexual feelings.Seventeen case series reporting on adverse events from RRM with or without reconstruction reported rates of unanticipated reoperations from 4% in those without reconstruction to 64% in participants with reconstruction.In women who have had cancer in one breast, removing the other breast may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM. AUTHORS' CONCLUSIONS: While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, BRCA1/2 carriers. CRRM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that CRRM improves survival, and studies that control for multiple confounding variables are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention when considering RRM.

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.

Comparison of prognosis and clinical features between synchronous bilateral and unilateral breast cancers.

PURPOSE: The clinical significance of synchronous bilateral breast cancer (SBBC) is unclear and its influence on prognosis is controversial. Our study objective was to determine the epidemiological features, tumor characteristics, and prognosis of SBBC in comparison with those of unilateral breast cancer (UBC). METHODS: A total of 3675 breast cancer patients diagnosed and treated between 2000 and 2014 were evaluated. Of these patients, 132 (3.6%) had bilateral breast cancer, including 55 patients (1.5%) with SBBC and 77 (2.1%) with metachronous bilateral breast cancer (MBBC). The patient demographic characteristics, including survival data and clinicopathological tumor characteristics, were obtained from medical charts and compared between the patients with SBBC and those with UBC. RESULTS: The median age in the SBBC group was 51 years (range 32-77). The mastectomy rate was higher in the SBBC group (72.7%) than in the UBC group (66.6%) (p=0.08). In both the SBBC and UBC groups, the baseline clinicopathological features and the history of treatment with radiotherapy and chemotherapy were similar. Infiltrating ductal carcinoma was the most common histology in both groups. Lobular histology was more frequent in the SBBC group (36.3%) than in the UBC group (17.1%; p<0.001). Stage IV disease at initial presentation was more frequent in the SBBC group than in the UBC group (34.5 vs 8.7%, p<0.001). The 5-year disease-free survival (DFS) rates were 90% and 82% in the SBBC and UBC groups, respectively (p=0.99). The 5-year overall survival (OS) rates were 83% and 88%, respectively (p=0.357). The multivariate Cox regression analysis, including stage, hormone receptor status, grade, and SBBC, revealed that the presence of SBBC was not associated with OS (hazard ratio 0.929; 95% confidence interval, 0.455-0.1894, p=0.839). CONCLUSION: Despite the differences in histology, initial stage, and other characteristics, the prognoses of UBC and SBBC were similar.

Helical Tomotherapy versus Conventional Technique for Post Mastectomy Left Sided Breast Cancer; Dosimetric Study.

PURPOSE: To evaluate the feasibility of using Helical Tomotherapy (HT) for post mastectomy left-sided breast cancer. METHODS AND MATERIALS: Treatment plans were generated for 5 post mastectomy left sided breast cancer patients treated at king Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia, comparing three-dimensional technique with the HT planning. The prescribed dose was 50 Gy in 25 fractions; the planning target volume (chest wall and nodal volumes) was contoured according to RTOG atlas and the heart, lungs, spinal cord and contralateral breast were contoured as Organs at Risks (OARs). RESULTS: Both plans achieved the planning criteria, however the HT plan increased the minimal dose to the PTV (78% vs. 45.4%, p=0.043), improving the dose conformity (0.76 vs. 0.38, p=0.034) and dose homogeneity (1.05 vs. 1.2, p=0.08), while a three-dimensional technique has better V20 of lung (15.8% vs. 22.6%, p=0.04), Mean Lung Dose (7.6Gy vs. 13.8Gy, p=0.043), contralateral breast dose (0.1 vs. 12.7, p=0.043) and comparable Mean Heart Dose (4.4Gy vs. 5.3Gy, p=0.136). CONCLUSION: Both plans achieved comparable target coverage and OARs sparing, however HT plans provided better dose conformity and homogeneity than did the three-dimensional plans at the cost of less sparing of the heart, left lung and contralateral breast for treatment of left-sided post mastectomy breast cancer.

[Clinicopathological characteristics and prognostic analysis of bilateral primary breast cancer].

OBJECTIVE: The aim of this study is to explore the clinicopathological characteristics, diagnosis, multidiscipline therapy and prognosis of bilateral primary breast cancer (BPBC). METHODS: Clinical data of 133 patients with BPBC seen in Cancer Institute and Hospital of Tianjin Medical University from January 2005 to December 2008 were retrospectively analyzed and compared with those of 266 patients with unilateral primary breast cancer (UPBC). RESULTS: BPBC accounted for 2.08% of all breast cancer cases. Compared with UPBC, BPBC patients had earlier menarche, more postmenopause disease and fewer fertility(P<0.05). The T stage, pathological type, histological grade and tumor stage of the second tumor in BPBC patients were significantly different from those in UPBC cases (P<0.05). The ER and HER-2 status of both the two tumors in BPBC and the PR status of the second tumor in BPBC were also significantly different from those in UPBC(P<0.05). Besides, the menopause status when the first tumor happened and the lymph node metastasis status when the second tumor occurred were independent prognostic factors. There was no significant difference between the five-year disease free survival rates of UPBC and BPBC (79.3% and 72.8%, P>0.05), but the 5-year overall survival rates of UPBC and BPBC had significant difference(89.8% and 84.9%, P=0.02). CONCLUSIONS: The prognosis of UPBC and BPBC has significant differences. If the patient is premenopause when the first tumor occurs or had more than ten metastatic axillary lymph nodes in patient with the second one, she has a poorer prognosis. The pationts who underwent unilateral breast radical mastectomy have an increased risk of contralateral breast cancer. In order to have early detection, diagnosis and treatment, we should strengthen the follow-up of the high risk patients.

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.

Bilateral breast cancer, synchronous and metachronous; differences and outcome.

The aims of this study were twofold: to analyze the incidence of patients having synchronous or metachronous bilateral invasive breast cancer (SBBC and MBBC) and to assess the characteristics and outcome compared to those having unilateral breast cancer (UBC). The used data were obtained from our prospective population-based cohort study which had been started in 1983. Bilateral breast cancer (BBC) was categorized as SBBC (≤3 months of the first primary) or MBBC (>3 months after the first primary). The incidence of SBBC was 1% and that of MBBC 7.0 %. Patients with UBC showed more ductal carcinoma compared to patients with BBC. MBBC status was an independent significant predictor of local failure (HR 1.9; 95% CI 1.3-2.7). SBBC status was an independent predictor of distant metastases (HR 2.6; 95% CI 1.4-4.5). Overall survival (OS) was better for MBBC (HR 0.6; 95% CI 0.4-0.8) and worse for SBBC (HR 2.3; 95% CI 1.5-3.6) compared to UBC. We noted: (1) MBBC showed a significant higher local failure compared to UBC, (2) SBBC, compared to MBBC and UBC had a significant higher distant metastases rate, (3) disease-specific survival and OS were significantly worse for SBBC compared to UBC and MBBC, and (4) that the OS for MBBC compared to UBC, was significantly better.