Impact of neoadjuvant compared to adjuvant chemotherapy on prognosis in patients with hormone-receptor positive / HER2-negative breast cancer: A propensity score matching population-based study.

BACKGROUND: The aim of this population-based cohort study was to investigate the impact of neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy in prognosis among patients with HR+/HER2 negative breast cancer. METHOD: This population-based study utilized data from the research database BCBaSe 3.0, based on the Swedish National Quality breast cancer register, including all patients with breast cancer diagnosis in Sweden between 2008 and 2019. Propensity score matching approach was applied. The outcomes of interest consisted of distant-disease free (DDFS), breast-cancer specific (BCSS), and overall survival (OS). RESULTS: In total, 14 459 patients were included in the study cohort of whom 2086 received NACT. After 1:1 propensity score matching (PSM), 1539 patients in each study group were available for analyses. No statistically significant difference in survival outcomes were observed between patients treated with NACT compared to those treated with adjuvant chemotherapy (Hazard Ratio (HR) for DDFS: 1.20; 95 % CI: 0.80-1.79; HR for BCSS: 1.16; 95 % CI: 0.54-2.49; HR for OS: 1.14; 95 % CI: 0.64-2.05). CONCLUSION: In this population-based cohort study of patients with HR+/HER2-breast cancer, the use of NACT seems to be comparable to adjuvant chemotherapy in terms of prognosis, although non-inferiority cannot be proven by this study design. Until further evidence suggesting a survival benefit in favor of either treatment is available, NACT can be pursued when surgical-de-escalation is intended.

Intraoperative Radiation Therapy Delivered by Brachytherapy in Breast Cancer: An Interim Analysis of a Phase 2 Trial.

PURPOSE: Intraoperative breast cancer radiotherapy (IORT) offers an alternative to external beam radiotherapy (EBRT) after breast-conserving surgery (BCS). The Intraoperative brachytherapy (IOBT) trial applies high dose rate (HDR) brachytherapy with a new applicator prototype as IORT after BCS. In this interim analysis of the IOBT trial, we present the oncological safety and toxicity of the method METHODS: Eligible patients were women, ≥ 50 years old with an unifocal nonlobular, estrogen-receptor-positive, HER2-negative breast cancer, cN0, ≤ 3 cm, treated with BCS and sentinel node biopsy (SNB). Toxicity was registered according to the LENT-SOMA scale. Cumulative incidence of local (LR) and regional recurrence (RR) were calculated through cumulative incidence function whereas overall survival (OS) was illustrated through Kaplan-Meier curve. RESULTS: Until February 2023, 155 women (median age 68 years) were included in the trial. Twenty-nine women (18.7%) received supplemental EBRT, mostly due to positive SNB. Three-year cumulative incidence of LR and RR were 1.0% (CI 95 % 0.1%-2.3%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five- year cumulative incidence of LR and RR were 3.9% (CI 95% 1.8%-6.4%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five-year OS was 96.3% (CI 95% 93.6%-98.4%). Side effects were limited, low grade, and transient. CONCLUSION: Acknowledging the short median follow-up time at interim analysis, our initial results indicate that delivering IORT through HDR brachytherapy in carefully selected breast cancer patients is feasible and oncological safe so far. A long-term follow-up is essential to confirm the initial results.

Angiosarcoma in the breast: a population-based cohort from Sweden.

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.

Digitally distributed Yoga Intervention in Breast Cancer Rehabilitation (DigiYoga CaRe): protocol for a randomised controlled trial.

INTRODUCTION: Breast cancer is the most prevalent cancer among women. The treatment is extensive; in addition to surgery, various combinations of radiation therapy, chemotherapy and antibody and endocrine treatment can be applied. Cancer-related fatigue (CRF) is high in patients with breast cancer, peaking during chemotherapy, but may persist for several years. Physical activity has proven to be effective in reducing CRF in breast cancer rehabilitation, but many patients tend to be less active after the diagnosis. Yoga has a previously demonstrated effect on energy levels and digitally distributed yoga intervention can potentially increase accessibility in pandemic times and facilitate participation for patients susceptible to infection and those living far from organised rehabilitation opportunities. The purpose of this study, Digital Yoga Intervention in Cancer Rehabilitation (DigiYoga CaRe) is to investigate whether a 12-week digitally distributed yoga intervention can reduce CRF and stress, improve health-related quality of life (HRQL) and affect pro-inflammatory and metabolic markers in patients with breast cancer. METHODS AND ANALYSIS: This multicentre study will adopt a randomised controlled design including 240 persons after their breast cancer surgery. They will be randomised to a 12-week digitally distributed yoga intervention or to a control group. The intervention group practice yoga two times a week, one yoga class live-streamed to the patient's computer or mobile device and one prerecorded video class for self-training. The controls receive standardised care, gift cards for flowers and access to yoga video links after the data collection has ended. The primary analysis will be performed following the principle of intention to treat. Data will be collected by questionnaires, blood samples, accelerometers and interviews. ETHICS AND DISSEMINATION: The DigiYoga CaRe study was approved by the Regional Ethical Review Board in Lund. The final results of this study will be disseminated to conference, patient and public involvements and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04812652.

Intraoperative high dose rate brachytherapy during breast-conserving surgery: A prospective pilot study.

PURPOSE: To evaluate feasibility, quality of life, toxicity, and cosmetic outcome for intraoperative breast cancer brachytherapy after breast-conserving surgery using high dose rate brachytherapy. METHODS: Fifty-two consecutive women, ⩾50 years old, diagnosed with a unifocal non-lobular breast cancer ⩽3 cm, N0, underwent breast-conserving surgery and sentinel node biopsy. Twenty-five women received intraoperative brachytherapy pre-pathology at primary surgery and the others post-pathology, during a second procedure. An applicator, connected to a high dose rate afterloader, was used. Two of the women were excluded due to metastases found per-operatively at a frozen section from the sentinel node. Quality of life was evaluated using two validated health questionnaires. Treatment toxicity was documented according to the LENT-SOMA scale by two oncologists. The cosmetic result was evaluated using the validated freely available software BCCT.core 2.0. RESULTS: The clinical procedure worked out well logistically. Seven women received supplementary external radiotherapy due to insufficient margins and, in one case, poor adaptation of the breast parenchyma to the applicator. No serious adverse effects from irradiation were registered. The results from the health questionnaires showed no major differences compared with reference groups from the Swedish population. Only two women were registered as having a "poor" cosmetic result while a majority of the women had a "good" outcome. CONCLUSIONS: This pilot study shows that intraoperative brachytherapy is a feasible procedure and encourages further trials evaluating its role in treatment of early breast cancer.

Influence of the subtype on local recurrence risk of breast cancer with or without radiation therapy.

PURPOSE: To investigate if intrinsic subtypes of breast cancer predict different risks of ipsilateral breast tumor recurrence (IBTR) following breast-conserving surgery (BCS) with and without postoperative radiation therapy. PATIENTS AND METHODS: We randomized 381 women with a unifocal T1N0M0 breast cancer to BCS alone (197 women) or BCS plus postoperative radiation therapy (XRT) (184 women). All available histopathological material was re-analyzed with modern immunohistochemical methods (223 women). After 20 years of complete follow-up we analyzed the risk of IBTR by intrinsic breast cancer subtypes (luminal A, luminal B/HER2-negative, luminal B/HER2-positive, HER2-positive and triple negative). We used Cox regression analyses to estimate hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: In a multivariate analysis the luminal B/HER2-negative subtype, compared with the luminal A subtype, was associated with a higher risk of IBTR overall (HR 3.04; 95% CI 1.38-6.71) and in both the XRT-group (HR 5.08 95% CI 1.31-19.7) and the non-XRT-group (HR 2.58 95%CI 1.07-6.20); (p for interaction = 0.37). The risk of IBTR in the XRT- and non-XRT group, stratified by intrinsic subtype, revealed an absolute risk difference at 20 years to the benefit of XRT of 14% (95% CI 1.0%-26%) for luminal A, 17% (95% CI -6.0% to 39%) for luminal B/HER2 negative and 22% (95% CI -7.0-51%) for the high-risk group. CONCLUSIONS: Among breast cancer patients treated with BCS, the luminal B/HER2-negative subtype predicts an about 3-fold higher risk for IBTR compared to other intrinsic subtypes independent of postoperative radiation therapy.

Omitting radiotherapy in women ≥ 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe.

PURPOSE: The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET). PATIENTS AND METHODS: Eligibility criteria were: consecutive patients with age ≥65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival. RESULTS: Between 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65-90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%). CONCLUSION: BCS and ET without RT seem to be a safe treatment option in women ≥ 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors.

Sector resection with or without postoperative radiotherapy for stage I breast cancer: 20-year results of a randomized trial.

PURPOSE: To investigate how radiotherapy (XRT) adds to tumor control using a standardized surgical technique with meticulous control of surgical margins in a randomized trial with 20 years of follow-up. PATIENTS AND METHODS: Three hundred eighty-one women with pT1N0 breast cancer were randomly assigned to sector resection with (XRT group) or without (non-XRT group) postoperative radiotherapy to the breast. With follow-up through 2010, we estimated cumulative proportion of recurrence, breast cancer death, and all-cause mortality. RESULTS: The cumulative probability of a first breast cancer event of any type after 20 years was 30.9% in the XRT group and 45.1% in the non-XRT group (hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.82). The benefit of radiotherapy was achieved within the first 5 years. After 20 years, 50.4% of the women in the XRT group died compared with 54.0% in the non-XRT group (HR, 0.92; 95% CI, 0.71 to 1.19). The cumulative probability of contralateral cancer or death as a result of cancer other than breast cancer was 27.1% in the XRT group and 24.9% in the non-XRT group (HR, 1.17; 95% CI, 0.77 to 1.77). In an anticipated low-risk group, the cumulative incidence of first breast cancer of any type was 24.8% in the XRT group and 36.1% in the non-XRT group (HR, 0.61; 95% CI, 0.35 to 1.07). CONCLUSION: Radiotherapy protects against recurrences during the first 5 years of follow-up, indicating that XRT mainly eradicates undetected cancer foci present at primary treatment. The similar rate of recurrences beyond 5 years in the two groups indicates that late recurrences are new tumors. There are subgroups with clinically relevant differences in risk.