BACKGROUND:Large randomized studies show equivalent survival after breast-conserving surgery (BCS) + adjuvant radiotherapy (RT) and mastectomy. In contrast, more recent observational studies suggest BCS + RT to be superior, but it is questionable whether patients in these treatment arms are comparable. Here, overall survival (OS) and breast cancer-specific survival (BCSS) after BCS + RT and mastectomy are compared within a randomized trial comparing intravenous and inhalation anaesthesia during breast cancer surgery. METHODS:The patient cohort was recruited from the randomized CAN-study. Patients with tumours >30 mm, patients with tumours <10 mm, and patients who underwent BCS without RT were excluded. OS and BCSS were estimated using multivariable Cox regression analyses and three different propensity score models. RESULTS:The final study cohort included 830 women, of whom 601 underwent BCS + RT (median age 64 years) and 229 underwent mastectomy (median age 68 years). Women who underwent mastectomy had more co-morbidities and more unfavourable tumour characteristics. Mastectomy was associated with significantly less favourable OS in unadjusted, adjusted, and two of the three propensity score analyses. BCSS was inferior in the mastectomy group in the unadjusted analysis, with an HR of 2.27 (95% c.i. 1.20 to 4.30). In the adjusted and three propensity score analyses, BCSS was equal in the treatment groups, with an adjusted HR of 1.02 (95% c.i. 0.43 to 2.42). CONCLUSION:In this study, which was designed to approximate a randomized trial as closely as possible, no significant difference in BCSS was observed between BCS + RT and mastectomy. Differences in OS likely reflect occult selection bias of patients with higher co-morbidity burden to mastectomy.

BACKGROUND:The prognostic relevance of multifocal and multicentric breast cancer remains unclear and current staging systems do not consider focality. The aim of this study was to explore whether women with multifocal breast cancer have less favourable tumour characteristics and worse survival compared with women with unifocal breast cancer. METHODS:Patient and tumour characteristics were obtained from Breast Cancer Database Sweden 3.0, which includes data for all Swedish women diagnosed with invasive breast cancer between 2008 and 2019 and who underwent surgery. Overall and breast cancer-specific survival rates were calculated using the Kaplan-Meier method and multivariable analysis was used to identify independent predictors of survival using the Cox proportional hazard model. RESULTS:A total of 71 419 women were included in the study: 59 445 (83.2%) had unifocal breast cancer, 7286 (10.2%) had multifocal breast cancer with two invasive foci, and 4688 (6.6%) had multifocal breast cancer with three or more invasive foci. Multifocal breast cancer was associated with higher clinical T and N categories compared with unifocal breast cancer. The median follow-up time was 5.96 (interquartile range 3.078.80) years. The breast cancer-specific 10-year survival rates were 86.1% for women with multifocal breast cancer with three or more foci, 86.5% for women with multifocal breast cancer with two foci, and 88.4% for women with unifocal breast cancer. In a multivariable analysis adjusted for patient and tumour characteristics, the HR for breast cancer-specific death was 1.17 (95% c.i. 1.03 to 1.32) for women with multifocal breast cancer with three or more foci compared with women with unifocal breast cancer. There was no statistically significant difference in overall survival between the three groups. CONCLUSION:The present study suggests that focality provides prognostic information that is additional to that provided by traditional tumour characteristics.

BACKGROUND:This prospective cohort study aimed to assess whether postoperative radiotherapy could safely be omitted in women aged 65 years and older with low-risk, estrogen receptor-positive T1N0 breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy. METHODS:Eligible patients were women aged 65 years and older with unifocal, nonlobular, grade 1 or 2, estrogen receptor-positive, pT1N0 breast cancer treated with breast-conserving surgery and endocrine therapy for 5 years. Patients were followed up with mammography at least annually for 10 years. The primary endpoint was local recurrence. Secondary endpoints were contralateral breast cancer, recurrence-free survival, and overall survival. RESULTS:The final study cohort included 601 patients with a median age of 71 years (range = 65-90 years) and a median tumor size of 11 mm (range = 3-20 mm). Median follow-up time was 119 months (interquartile range = 103-121 months). The cumulative incidence of local recurrence was 1.5% (95% confidence interval [CI] = 0.8% to 2.8%) and 5.5% (95% CI = 3.8% to 7.6%) at 5 and 10 years, respectively. The cumulative incidence of contralateral breast cancer was 1.7% (95% CI = 0.9% to 3.0%) at 5 years and 4.5% (95% CI = 3.0% to 6.6%) at 10 years. The overall survival rate at 10 years was 83.1% (95% CI = 80.8% to 85.4%). In total, 3 (0.5%) patients died because of breast cancer. CONCLUSION:Our results support the possibility to omit radiotherapy after breast-conserving surgery in a well-defined subgroup of women aged 65 years and older with low-risk, estrogen receptor-positive, pT1N0 breast cancer receiving adjuvant endocrine therapy.

Abstract &gt;Multifocal breast cancer: tumor biology and prognostic importance Background The incidence of multifocal breast cancer (MBC) varies widely in the literature and recent reports indicate that the incidence of MBC is increasing. Several studies have shown similar tumor biology in the different foci of multifocal tumors, and it has been suggested that multifocal tumors may in fact be intramammary metastases and thus be a sign of a more aggressive cancer type than unifocal tumors. Knowledge regarding outcome and optimal treatment of MBC compared to unifocal breast cancer (UBC) is still limited. The aim of the present study was to explore if multifocal breast cancers have less favorable characteristics and prognosis compared to unifocal breast cancers. Method Patient and tumor characteristics were obtained from Breast Cancer database Sweden (BcBaSe3) including women with invasive breast cancer 2008-2019 who had undergone primary surgery. Women with distant metastases at time of diagnosis, women receiving neoadjuvant systemic therapy, and men were excluded. Overall- and breast cancer specific survival were calculated with Kaplan-Meier and Cox-regression analyses. Results A total of 71607 women met our inclusion criteria, 11961 (16.7%) with MBC and 59512 (83.3%) with UBC. Among women with MBC, 64.1% underwent mastectomy compared to 32.4% of women with UBC and 40.1% with MBC underwent complete axillary lymph node dissection compared to 23.5% of the women with UBC. MBC was associated with higher T-stage (T2 31.9% vs. 25.8% and T3 4.6% vs. 2.6%. p&lt; 0.001) and higher N-stage (N+ 13.7% vs. 8.4%, P&lt; 0.001), compared to UBC. MBC were more often of lobular type (18.8% vs. 12.4%, P&lt; 0.001), of higher grade (grade 3 29.3% vs. 27.3%, p&lt; 0.001), with positive hormone receptor status (88.4% vs. 86.7%, p&lt; 0.001), and Her2 positivity (13.3% vs. 10.9%, p&lt; 0.001). Adjuvant systemic treatment was more frequently administered to women with MBC, adjuvant chemotherapy (45.3% vs. 33.3%, p&lt; 0.001) and endocrine treatment (82.9% vs. 75.3%, p&lt; 0.001). Breast cancer specific 10- year survival was 86.4% and 88.5% for MBC and UBC respectively, hazard ratio for breast cancer death 1.19 (95 % confidence interval, 1.11- 1.28). Overall survival did not differ between the two groups (10-year survival 76.0%, p=0.35) Conclusion MBC appears to have a more aggressive tumor biology than UBC, with the exception of hormone receptor status and MBC is associated with decreased breast cancer specific survival. Further analysis of possible interactions with different treatment methods will be conducted. Citation Format: Emma Söderberg, Malin Sund, Fredrik Wärnberg, Hans Garmo, Anna-Karin Wennstig, Lars Holmberg, Greger Nilsson, Charlotta Wadsten. Multifocal breast cancer: tumor biology and prognostic importance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-07.

Introduction: Observational studies suggest that breast conserving surgery (BCS) and radiotherapy (RT) offers superior survival compared to mastectomy. The aim was to compare patient and tumour characteristics in women with invasive breast cancer ≤30 mm treated with either BCS or mastectomy, and to explore the underlying reason for choosing mastectomy. Methods: Women registered with breast cancer ≤30 mm and ≤4 positive axillary lymph nodes in the Swedish National Breast Cancer Register 2013–2016 were included. Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy vs. BCS. Results: Of 1860 breast cancers in 1825 women, 1346 were treated by BCS and 514 by mastectomy. Adjuvant RT was given to 1309 women (97.1 %) after BCS and 146 (27.6 %) after mastectomy. Variables associated with receiving a mastectomy vs. BCS included clinical detection (Odds Ratio (OR) 4.15 (95 % Confidence Interval (CI) 3.35–5.14)) and clinical stage (T2 vs. T1 (OR 3.68 (95 % CI 2.90–4.68)), N1 vs. N0 (OR 2.02 (95 % CI 1.38–2.96)). Women receiving mastectomy more often had oestrogen receptor negative, HER2 positive tumours of higher histological grade. The most common reported reason for mastectomy was large or multifocal tumours (53.5 %), followed by patient preference (34.5 %). Conclusion: Choice of surgery is strongly associated with key prognostic factors among women undergoing BCS with RT compared to mastectomy. Failure to control for all relevant confounders may bias results in outcome studies in favour of BCS.

Abstract Introduction Locally advanced breast cancer (LABC) refers to large primary breast tumours (T3), tumours of any size with chest wall/skin involvement (T4), and/or extensive lymph node involvement (N2-3). LABC may be a consequence of delayed presentation or aggressive tumour biology. The aim of the study was to explore patient characteristics, treatment, and time trends of LABC in a Swedish population-based cohort. Method The study cohort was retrieved from BCBaSe 3.0 including 94 271 patients with invasive breast cancer diagnosed 2008-2019 after exclusion of those with distant metastasis at diagnosis or within 3 months. Comparisons were made between non-LABC (T0-2N0-1) and LABC subcategorized by T-stage (T≥3) and N-stage (N≥2). Result Of all BC, 6565 (7.0 %) were LABC, with a fairly constant proportion over time. A higher proportion of LABC was seen both among the youngest (<40 y; 11.9 %) and among the oldest (80+ y; 15.7 %), and in those with a low level of education (9.5 %). Lobular BC was overrepresented among LABC (16.0 % vs 11.1 % in non-LABC), as were the Her2-positive (17.3 % vs 10.2 %) and triple-negative subtypes (11.0 % vs 7.3 % in non-LABC). On average, 47.2 % of LABC underwent primary surgery, 44.2 % received neoadjuvant treatment ranging from 26.7 % for T0-2N2 to 83.0 % for inflammatory BC, whereas 8.6 % received no treatment. Of those undergoing neoadjuvant treatment, 71.8 % proceeded to surgery. Discussion LABC encompasses a wide range of tumours, comprising both primarily operable and non-operable tumours, with notable distinctions observed between different subgroups of LABC.

BACKGROUND:Breast angiosarcoma is a rare disease mostly observed in breast cancer (BC) patients who have previously received radiotherapy (RT). Little is known about angiosarcoma aetiology, management, and outcome. The study aim was to estimate risk and to characterize breast angiosarcoma in a Swedish population-based cohort.METHODS:The Swedish Cancer Registry was searched for breast angiosarcoma between 1992 and 2018 in three Swedish healthcare regions (population 5.5 million). Information on previous BC, RT, management, and outcome were retrieved from medical records.RESULTS:Overall, 49 angiosarcomas located in the breast, chest wall, or axilla were identified, 8 primary and 41 secondary to BC treatment. Median age was 51 and 73 years, respectively. The minimum latency period of secondary angiosarcoma after a BC diagnosis was 4 years (range 4-21 years). The cumulative incidence of angiosarcoma after breast RT increased continuously, reaching 1.4‰ after 20 years. Among 44 women with angiosarcoma treated by surgery, 29 developed subsequent local recurrence. Median recurrence-free survival was 3.4 and 1.8 years for primary and secondary angiosarcoma, respectively. The 5-year overall survival probability for the whole cohort was 50 per cent (95 per cent c.i., 21 per cent-100 per cent) for primary breast angiosarcoma and 35 per cent (95 per cent c.i., 23 per cent-54 per cent) for secondary angiosarcoma.CONCLUSION:Breast angiosarcoma is a rare disease strongly associated with a history of previous BC RT. Overall survival is poor with high rates of local recurrences and distant metastasis.

Background: Mastectomy (Mx) and breast conserving surgery (BCS) when combined with adjuvant whole breast radiotherapy (RT) have been shown to give equivalent outcome in randomized trials . In recent years, a number of retrospective population-based studies suggest that BCS offers superior survival compared to Mx. In these studies, treatment has not been randomized, but selected based on patient and tumour characteristics or patient´s own choice. The aim of this study was to compare clinicopathological variables in women with tumours less than 30mm in size treated with either BCS or Mx, where both surgical methods would have been feasible based on postoperatively recorded tumour characteristics. Our second aim was to explore the underlying reason for choosing Mx as surgical approach. Method: The study is a population-based retrospective analysis of prospectively collected data from the Swedish National Breast Cancer Register (NBCR). The source population are women registered with primary invasive breast cancer with a tumour size up to 30 mm and no more than four positive axillary lymph nodes, treated between 2013-2016 in the northern health care region in Sweden. During this time period, the reason for selecting Mx was registered in this region with five optional alternatives: 1.Age < 40 years, 2.Large tumour size/extent relative breast volume, 3.Multifocality/multicentricity, 4.RT contraindicated due to comorbidity and 5.Patient´s own choice. All cases with male breast cancer and patients treated with neoadjuvant therapy were excluded.Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy shown as odds ratios with 95% confidence intervals (CI). Results: A total of 1860 women met our inclusion criteria, 1346 of which had undergone BCS (mean age 63) and 514 Mx (mean age 66). For 1309 women (97.1%) in the BCS group and 146 (27.6%) in the Mx group adjuvant RT was added to the breast, chest wall and/or ipsilateral regional lymph nodes after surgery. Clinical detection, OR 3.35 (95%CI 3.32-5.14), higher T stage OR 2.66 (2.00-3.54), N stage OR 1.84 (1.46-2.32) and multifocality, OR 4.59 (3.56-5.92) were associated with a higher likelihood of receiving Mx. Women treated with Mx had more lobular tumours, OR 1.42 (1.05-1.92), higher grade, OR 2.27 (1.65-3.13), more hormone receptor negative, 1.47 (1.09-1.98) and HER2 positive tumours, OR 1.61 (1.19-2.17) compared to women treated with BCS.The most common reason for choosing Mx was large tumour size and/or multifocality (52.8%). The second most common reason was the woman´s own preference (36.6%). In 9 % of the cases RT was considered contraindicated, hence Mx was recommended by the treating surgeon or tumour board. Conclusion: Women with invasive breast cancer up to 30mm selected for treatment with Mx have less favourable prognostic characteristics than those treated with BCS. Selection bias may largely explain the survival benefits of BCS compared to Mx demonstrated in observational studies. Table 1: Distribution of factors listed as reason of mastectomy as surgical treatment. Table based on a a total of 431 mastectomy cases where reason for Mx were listed. RT = Radiotherapy No. of patients%Age < 40 years61.4large tumour size/extent relative breast volume13531.3Multifocality/multicentricity9321.5RT contraindicated due to comorbidity399.0Patients own choice15836.6 Citation Format: Emma Söderberg, Malin Sund, Fredrik Wärnberg, Lars Holmberg, Greger Nilsson, Hans Garmo, Carl Blomqvist, Charlotta Wadsten. The association of clinicopathological variables and patient´s preference with surgical decision-making for early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-02.

To investigate if molecular subtype is associated with outcome in stage 1 breast cancer (BC). Tissue samples from 445 women with node-negative BC ≤ 15 mm, treated in 1986–2004, were classified into surrogate molecular subtypes [Luminal A-like, Luminal B-like (HER2−), HER2-positive, and triple negative breast cancer (TNBC)]. Information on treatment, recurrences, and survival were gathered from medical records. Tumour subtype was not associated with overall survival (OS). Luminal B-like (HER2−) and TNBC were associated with higher incidence of distant metastasis at 20 years (Hazard ratio (HR) 2.26; 95% CI 1.08–4.75 and HR 3.24; 95% CI 1.17–9.00, respectively). Luminal B-like (HER2−) and TNBC patients also had worse breast cancer-specific survival (BCSS), although not statistically significant (HR 1.53; 95% CI 0.70–3.33 and HR 1.89; 95% CI 0.60–5.93, respectively). HER2-positive BC was not associated with poor outcome despite no patient receiving HER2-targeted therapy, with most of these tumours being ER+. Stage 1 TNBC or Luminal B-like (HER2−) tumours behave more aggressively. Women with HER2+/ER+ tumours do not have an increased risk of distant metastasis or death, absent targeted treatment.

PURPOSE Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer. METHODS The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients. RESULTS The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor–negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF. CONCLUSION Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.

Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of later radiation-induced lung cancer (LC). We examined the risk of primary LC in a population-based cohort of 52300 women treated for BC during 1992 to 2012, and 253796 age-matched women without BC. Cumulative incidence of LC was calculated by the Kaplan–Meier method, and the risk of LC after BC treatment was estimated by Cox proportional hazards regression analyses. Women with BC receiving RT had a higher cumulative incidence of LC compared to women with BC not receiving RT and women without BC. This became apparent 5 years after RT and increased with longer follow-up. Women with BC receiving RT had a Hazard ratio of 1.59 (95% confidence interval 1.37–1.84) for LC compared to women without BC. RT techniques that lower the incidental lung doses, e.g breathing adaption techniques, may lower this risk.

Background Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC. Methods The Breast Cancer DataBase Sweden (BCBaSe) includes all women diagnosed with BC from 1992 to 2012 ( n = 60,217) and age-matched women without a history of BC ( n = 300,791) in three Swedish health care regions. Information on comorbidity, educational level, and incidence of IHD was obtained through linkage with population-based registries. The risk of IHD was estimated by Cox proportional hazard regression analyses and cumulative incidence by the Kaplan-Meier method. Results Women with BC had a lower risk of IHD compared to women without BC with a hazard ratio (HR) of 0.91 (95% CI 0.88–0.95). When women with left-sided BC were compared to right-sided BC, an increased HR for IHD of 1.09 (95% CI 1.01–1.17) was seen. In women receiving RT, a HR of 1.18 (95% CI 1.06–1.31) was seen in left-sided compared to right-sided BC, and the HRs increased with more extensive lymph node involvement and with the addition of systemic therapy. The cumulative IHD incidence was increased in women receiving left-sided RT compared to right-sided RT, starting from the first years after RT and sustained with longer follow-up. Conclusions Women given RT for left-sided BC during 1992 to 2012 had an increased risk of IHD compared to women treated for right-sided BC. These women were treated in the era of three-dimensional conformal RT (3DCRT), and the results emphasize the importance of further developing and implementing RT techniques that lower the cardiac doses, without compromising the beneficial effects of RT.

To assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC). The study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient’s original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location. The odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) (p = 0.005). Women receiving mean doses of 1–5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47–1.74) for a later coronary intervention compared to women receiving mean doses of 0–1 Gy to the mid LAD. In women receiving mean doses of 5–20 Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52–2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01–13.6) for mean doses over 20 Gy, when compared to women receiving mean doses of 0–1 Gy to the mid LAD. In women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS. The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992-2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed. Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82-1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60-0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53-1.37 for left-sided versus right-sided RT). The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.

IMPORTANCE:Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC).OBJECTIVE:To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2).DESIGN, SETTING, AND PARTICIPANTS:This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015.MAIN OUTCOMES AND MEASURES:Recurrence-free survival (RFS).RESULTS:Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively).CONCLUSIONS AND RELEVANCE:Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis.TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00114816.

PurposeTo determine the inter-observer variation in delineating the coronary arteries as organs at risk (OAR) in breast cancer (BC) radiotherapy (RT) and how this variation affects the estimated coronary artery radiation dose.MethodDelineation of the left main and the left anterior descending coronary artery (LMCA and LAD), and the right coronary artery (RCA), by using the heart atlas by Feng et al., was performed by three radiation oncologists in 32 women who had received adjuvant RT for BC. Centres of the arteries were calculated and distances between artery centres were measured and the artery radiation doses were estimated. The intraclass correlation coefficient (ICC) was used to quantify the variability in doses.ResultsAlong the extent of RCA, the median distance between centres of arteries varied from 2 to 9mm with similar patterns over pairs of oncologists. For the LMCA-LAD the median distance varied from 1 to 4mm. The estimated maximum radiation doses showed an ICC variation from 0.82 to 0.97.ConclusionThe coronary arteries can be reliably identified and delineated as OARs in BC RT. The spatial variance is limited and the total variation in radiation dose is almost completely determined by the between patient variation.