Long-term follow-up after treatment of invasive and in situ breast cancer : aspects on second breast cancers HRQOL and lymphoedema

Breast cancer is the most frequent cancer among Swedish women and in 2012, 8490 new inva- sive breast cancers were diagnosed. The incidence of in situ breast cancer has markedly in- creased since nationwide mammography screening was introduced in the late 1980s. The in- creasing figures of in situ breast cancer are predominantly attributable to an increased frequency of ductal carcinoma in situ (DCIS). In 2012, 1443 in situ breast cancers were diagnosed in Swe- den, which is approximately 15% of all diagnosed breast cancers. The main aims of the first two papers were to study the long-term HRQOL after different types of surgical treatment in women with DCIS (paper I) and to study the risk of developing a new in situ or invasive breast cancer after a first in situ cancer in women with and without a family his- tory for breast cancer (paper II). Since the 1980s, breast-conserving surgery for DCIS has been recommended whenever feasible. Several randomised trials have shown a decreased rate of ipsi- lateral DCIS or invasive breast cancer recurrence through the addition of adjuvant radiotherapy. Mastectomy is still recommended for women with either multifocal DCIS, and/or unfavourable proportion between tumour size and breast volume. For these women an immediate breast re- construction (IBR) is an alternative to maintain a breast contour. As surgery is the primary treatment for this disease, it is essential to increase current understanding of its long-term con- sequences. In paper I, 162 women treated for DCIS with breast-conserving surgery with or without postoperative radiotherapy, or with mastectomy and IBR, had a satisfactory long-term HRQOL. However, body image appeared to be affected in women after mastectomy and IBR. Using the population-based Swedish Multi-Generation and Cancer Registers we identified 8,111 women (paper II) diagnosed with in situ breast cancer between 1980 and 2004. The risk of a subsequent invasive breast cancer was increased more than fourfold [SIR 4.55 (95% CI 4.23- 4.88)] among women with in situ breast cancer as compared to women in the general population and the risk for a contralateral in situ breast cancer was almost sixteenfold increased [SIR 15.98(95% CI, 13.23-19.14)]. Having a family history for breast cancer increased the risk for contralateral invasive breast cancer by almost 50 % [incidence rate ratio 1.47 (95% CI 1.05- 2.05)]. The risk for a subsequent invasive breast cancer, as well as mortality was substantially higher in younger women, which should be taken into account when planning their treatment and follow-up. The main aims of paper III and IV were to evaluate the impact of axillary surgery on arm lym- phoedema and long-term HRQOL. Axillary lymph node dissection (ALND) was the standard surgical procedure for staging well into the 1990s, when it was replaced by the sentinel lymph node biopsy (SLNB), in patients with preoperatively no signs of axillary metastases. In a multi- centre study, including 557 women, we showed that SLNB alone is associated with a minimal risk of increased arm volume and few self-perceived symptoms of arm lymphoedema, signifi- cantly less than after ALND, regardless of lymph node status. Yet, 20% of the women who un- derwent SLNB, reported symptoms of arm lymphoedema, which emphasizes the importance of performing SLNB strictly on patients who can benefit from the staging results. Three years after surgery women in all three study groups appeared to have a satisfactory HRQOL. Women reporting self-perceived arm lymphoedema, regardless of objective lymphoedema or not, re- ported poorer HRQOL than those women who did not, indicating that more attention should be given to the subjective reports of symptoms, in order to better help these women

Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial

Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.Peer reviewe

Complications after breast augmentation with dermal fillers containing copolyamide: A systematic review

Background: Dermal fillers containing copolyamide are used for breast augmentation and are marketed under different labels, such as Aquafilling, Los Deline, Aqualift, and Activegel. In recent years, the number of publications reporting complications after use of these fillers has increased. Methods: Through a computerized search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of published studies on complications, treatment options, and radiological findings related to breast augmentation with dermal fillers containing copolyamide was performed. Publications between January 1, 2007, and January 23, 2023, were included. Retrieved studies were screened for inclusion and quality assessment. The Joanna Briggs checklist for case reports and the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cross-sectional studies were used. Results: Sixteen studies met the inclusion criteria: 14 case reports and 2 retrospective cohort studies, including 196 women and 333 complications. Long-term complications (≥30 days after surgery) were described in 15 studies. The most commonly reported complications were nodules in the breast (130 patients), pain (92 patients), inflammation and/or infection (43 patients), breast deformities (35 patients), and migration of the filler to the pectoralis muscle, abdominal wall, thoracic wall, pubic area, back, or upper extremity (27 patients). The median time between injection of the dermal filler and any complication was 18 months, and the majority of patients with complications required surgical intervention. Conclusion: Given the reports of severe complications months to years after injection of dermal fillers containing copolyamide and the lack of studies evaluating long-term safety, our interpretation is that dermal fillers containing copolyamide should not be used for breast augmentation

The impact of in situ breast cancer and family history on risk of subsequent breast cancer events and mortality - a population-based study from Sweden

BACKGROUND: The clinical behavior of in situ breast cancer is incompletely understood and several factors have been associated with invasive recurrence. The purpose of this study was to evaluate long-term risk of subsequent breast cancer and mortality among women diagnosed with in situ breast cancer, in relation to family history METHODS: Using the population-based Swedish Multi-Generation and Cancer Registers we identified 8111 women diagnosed with in situ breast cancer between 1980 and 2004. We used standardized incidence ratios (SIRs) to measure the relative risk of subsequent invasive or contralateral in situ breast cancer and standardized mortality ratios (SMRs) for relative risks of death. RESULTS: Among women diagnosed with in situ breast cancer, the cumulative 10-year and 20-year risk for subsequent contralateral or ipsilateral invasive cancer was approximately 10 % and 18 %, respectively. The risk of subsequent invasive breast cancer was increased more than 4-fold (SIR 4.6 (95 % CI 4.2 - 4.9)) among women with in situ breast cancer as compared to women in the general population and the risk of contralateral in situ breast cancer was increased almost 16-fold (SIR 16.0 (95 % CI 13.2-19.1)). Having a family history of breast cancer increased the risk of contralateral invasive breast cancer by almost 50 % (incidence rate ratio 1.5 (95 % CI 1.0-2.0)). Women under forty years old at diagnosis, without family history, had a 7-fold increased risk, and those with a family history had a 14-fold increased risk for subsequent invasive breast cancer with SIRs of 7.2 (95 % CI 4.8-10.5) and 14.3 (95 % CI 7.4-25.0), respectively. The overall risk of death in women with in situ breast cancer was significantly increased by 30 % compared to the general population but was highly dependent on the occurrence of a second invasive cancer event (SMR 1.3 (95 % CI 1.2-1.4)). CONCLUSIONS: Among women with in situ breast cancer, a positive family history increases the risk of contralateral invasive breast cancer by almost 50 %. The risk of subsequent invasive breast cancer and mortality is substantially higher in younger women, which should be taken into account when planning their treatment and follow up

The impact of in situ breast cancer and family history on risk of subsequent breast cancer events and mortality - a population-based study from Sweden

BACKGROUND: The clinical behavior of in situ breast cancer is incompletely understood and several factors have been associated with invasive recurrence. The purpose of this study was to evaluate long-term risk of subsequent breast cancer and mortality among women diagnosed with in situ breast cancer, in relation to family history METHODS: Using the population-based Swedish Multi-Generation and Cancer Registers we identified 8111 women diagnosed with in situ breast cancer between 1980 and 2004. We used standardized incidence ratios (SIRs) to measure the relative risk of subsequent invasive or contralateral in situ breast cancer and standardized mortality ratios (SMRs) for relative risks of death. RESULTS: Among women diagnosed with in situ breast cancer, the cumulative 10-year and 20-year risk for subsequent contralateral or ipsilateral invasive cancer was approximately 10 % and 18 %, respectively. The risk of subsequent invasive breast cancer was increased more than 4-fold (SIR 4.6 (95 % CI 4.2 - 4.9)) among women with in situ breast cancer as compared to women in the general population and the risk of contralateral in situ breast cancer was increased almost 16-fold (SIR 16.0 (95 % CI 13.2-19.1)). Having a family history of breast cancer increased the risk of contralateral invasive breast cancer by almost 50 % (incidence rate ratio 1.5 (95 % CI 1.0-2.0)). Women under forty years old at diagnosis, without family history, had a 7-fold increased risk, and those with a family history had a 14-fold increased risk for subsequent invasive breast cancer with SIRs of 7.2 (95 % CI 4.8-10.5) and 14.3 (95 % CI 7.4-25.0), respectively. The overall risk of death in women with in situ breast cancer was significantly increased by 30 % compared to the general population but was highly dependent on the occurrence of a second invasive cancer event (SMR 1.3 (95 % CI 1.2-1.4)). CONCLUSIONS: Among women with in situ breast cancer, a positive family history increases the risk of contralateral invasive breast cancer by almost 50 %. The risk of subsequent invasive breast cancer and mortality is substantially higher in younger women, which should be taken into account when planning their treatment and follow up

Additional file 1: Table S1. of The impact of in situ breast cancer and family history on risk of subsequent breast cancer events and mortality - a population-based study from Sweden

Excess additive risks (EAR) per 10,000 person-years after diagnosis of first in situ breast cancer, presented stratified by year at first diagnosis, age at first diagnosis, time since first diagnosis and family history. (DOC 45 kb

Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases – an open, multicentre, randomised non-inferiority phase 3 trial

Introduction Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.Methods and analysis In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I–III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.Ethics and dissemination The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.Trial registration number NCT05634889

Multidisciplinary management of phyllodes tumours and breast sarcoma : a cross-sectional survey of clinical practice across the United Kingdom and Ireland

Aims Phyllodes tumours and breast sarcomas are uncommon tumours and their rarity poses significant challenges in diagnosis and management. This cross-sectional study was conducted to evaluate the multidisciplinary clinical practice for these tumours across the UK and Ireland, with the aim of identifying gaps in knowledge and providing direction for establishing national guidelines. Materials and methods An international survey was adapted and circulated to breast and/or sarcoma surgeons and oncologists in the UK and Ireland through national organisations. Multidisciplinary team (MDT) responses were analysed anonymously. Results Twenty-eight MDTs participated in this study, predominately from high-volume units (85.5%). Although only 43% of the surveyed units were part of a trust that holds a sarcoma MDT, 68% of units managed malignant phyllodes and angiosarcoma, whereas 64.5% managed soft-tissue sarcoma of the breast. Across all subtypes, axillary surgery was recommended by 14–21% of the MDTs and the most recommended resection margins for breast surgery were ‘no tumour on ink’ in benign phyllodes (39%) and 10 mm in the remaining subtypes (25–29%). Immediate breast reconstruction was supported by 11–18% of MDTs for breast sarcoma subtypes, whereas 36% and 32% advocated this approach in benign and borderline phyllodes tumours, respectively. Adjuvant radiotherapy and chemotherapy were recommended by up to 29% and 11% of the MDTs, respectively. Conclusion The results of this study demonstrate a wide variation in clinical practice across the surveyed MDTs. As only 28 MDTs participated in our study, with under-representation from low-volume units, our results might be an underestimation of the variability in practice across the UK and Ireland. This multi-institutional study sheds light on controversial aspects in the management of phyllodes tumours and breast sarcoma, identifies the need for national guidelines to inform best practice, and calls for the centralisation of the management of breast sarcoma within specialist centres

Current clinical practice in the management of phyllodes tumors of the breast : an international cross-sectional study among surgeons and oncologists

PurposePhyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking.MethodsWe conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents.ResultsA total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types.ConclusionsThis study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.Peer reviewe