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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.

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.

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.

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.

Purpose To investigate if molecular subtype is associated with outcome in stage 1 breast cancer (BC). Methods 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. Results 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+. Conclusions 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.

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.

Background: 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).

Methods: 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.

Results: 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 0-1Gy to the mid LAD. In women receiving mean doses of 5-20Gy 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 20Gy, when compared to women receiving mean doses of 0-1Gy to the mid LAD.

Conclusions: 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.

Background

Neoadjuvant therapy (NAT) for operable breast cancer may facilitate more breast-conserving surgery (BCS). It seems, however, that this benefit is not being realized fully.

Methods

A systematic review of the literature was performed. RCTs were included. The criteria for inclusion were: documentation of surgical assessment before and after NAT, surgery performed (BCS or mastectomy), and clinical and pathological responses.

Results

A total of 1452 patients from seven RCTs met the inclusion criteria. After NAT, the feasibilityof BCS increased from 43⋅3to60⋅4 per cent (P < 0⋅001), but BCS was performed in only 51⋅8percent(P = 0⋅04). Only 31 per cent of patients who became eligible for BCS (assessed on clinical response)underwent BCS (pooled rate ratio 0⋅31, 95 per cent c.i. 0⋅22 to 0⋅44; P < 0⋅001). Of the mastectomycandidates who achieved a pathological complete response after NAT, only 41 per cent underwent BCS(pooled rate ratio 0⋅41, 0⋅23 to 0⋅74; P = 0⋅003). The main factors that influenced the decision not to shiftto BCS, even though it was feasible, were clinical assessment before NAT, multicentricity and tumoursize at presentation.

Conclusion

Breast surgery performed after NAT does not reflect tumour response, resulting in potentially unnecessary radical surgery, especially mastectomy. The barriers to maximizing the surgical benefits of NAT need to be better understood and explored. Still unnecessary mastectomies