Breast Surgery
Cohort Study: Levonorgestrel IUD Use Linked to Increased Breast Cancer Risk in Premenopausal Women
20 Oct, 2024 | 18:13h | UTCBackground: Levonorgestrel-releasing intrauterine systems (LNG-IUSs) are increasingly used, especially among Danish premenopausal women over 30 years old, as a preferred method of hormonal contraception. Previous studies have suggested an increased risk of breast cancer with LNG-IUS use but did not adequately address the duration of continuous use or account for other hormonal contraceptive exposures.
Objective: To assess the risk of breast cancer associated with continuous use of LNG-IUSs, accounting for other hormonal exposures.
Methods: In this nationwide Danish cohort study, 78,595 first-time LNG-IUS users aged 15–49 years from 2000 to 2019 were identified and matched 1:1 by birth year to nonusers of hormonal contraceptives. Exclusion criteria included prior hormonal contraceptive use within 5 years, previous cancer, postmenopausal hormone therapy, and pregnancy at baseline. Participants were followed from initiation until breast cancer diagnosis, other cancer, pregnancy, hormone therapy initiation, emigration, death, or December 31, 2022. Cox proportional hazards models adjusted for confounders estimated hazard ratios (HRs) for breast cancer associated with continuous LNG-IUS use.
Results: During a mean follow-up of 6.8 years, 1,617 breast cancer cases occurred: 720 among LNG-IUS users and 897 among nonusers. The mean age was 38 years. Continuous LNG-IUS use was associated with a higher breast cancer risk compared to nonuse (HR, 1.4; 95% CI, 1.2–1.5). HRs by duration were 1.3 (95% CI, 1.1–1.5) for 0–5 years, 1.4 (95% CI, 1.1–1.7) for >5–10 years, and 1.8 (95% CI, 1.2–2.6) for >10–15 years. Excess breast cancer cases per 10,000 users were 14 (95% CI, 6–23), 29 (95% CI, 9–50), and 71 (95% CI, 15–127), respectively. The trend test for duration was not statistically significant (P = .15).
Conclusions: Continuous use of LNG-IUSs was associated with an increased risk of breast cancer among women aged 15–49 years compared to nonuse of hormonal contraceptives. The absolute increase in risk was low.
Implications for Practice: Healthcare providers should inform women about the potential increased breast cancer risk associated with LNG-IUS use, especially considering its widespread and long-term use among premenopausal women. While the absolute risk increase is small, this information is essential for making informed contraceptive choices.
Study Strengths and Limitations: Strengths include the large, nationwide cohort and adjustment for multiple confounders. Limitations include potential underestimation of risk due to unrecorded LNG-IUS removals before the recommended duration, lack of a statistically significant trend with duration suggesting possible low statistical precision or non-causal association, and the possibility of unmeasured confounding.
Future Research: Further studies are needed to confirm these findings, clarify the causal relationship, and understand the mechanisms underlying the potential increased breast cancer risk with LNG-IUS use.
RCT: Pembrolizumab Plus Chemotherapy Improved Overall Survival in Early-Stage Triple-Negative Breast Cancer
18 Sep, 2024 | 16:08h | UTCBackground: Early-stage triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis. The phase 3 KEYNOTE-522 trial previously demonstrated that adding pembrolizumab to chemotherapy improved pathological complete response rates and event-free survival in this population.
Objective: To determine whether neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab improves overall survival compared to neoadjuvant chemotherapy alone in patients with early-stage TNBC.
Methods: In this multicenter, randomized, double-blind, placebo-controlled phase 3 trial (KEYNOTE-522), 1174 patients with previously untreated stage II or III TNBC were randomized 2:1 to receive neoadjuvant pembrolizumab (200 mg every 3 weeks) plus chemotherapy (paclitaxel and carboplatin, followed by doxorubicin–cyclophosphamide or epirubicin–cyclophosphamide) or placebo plus the same chemotherapy regimen. After surgery, patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary endpoints were pathological complete response and event-free survival; overall survival was a key secondary endpoint.
Results: After a median follow-up of 75.1 months, the estimated 5-year overall survival was 86.6% in the pembrolizumab–chemotherapy group versus 81.7% in the placebo–chemotherapy group (hazard ratio for death, 0.66; P=0.002). The 5-year event-free survival was 81.2% versus 72.2%, respectively (hazard ratio for event or death, 0.65; 95% CI, 0.51–0.83). Grade 3 or higher treatment-related adverse events occurred in 77.1% of patients receiving pembrolizumab–chemotherapy and 73.3% receiving placebo–chemotherapy. Serious treatment-related adverse events occurred in 34.1% and 20.1% of patients, respectively.
Conclusions: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab significantly improved overall survival compared to chemotherapy alone in patients with early-stage TNBC.
Implications for Practice: The addition of pembrolizumab to standard neoadjuvant chemotherapy, followed by adjuvant pembrolizumab, should be considered a new standard of care for patients with high-risk, early-stage TNBC, offering a significant survival benefit.
Study Strengths and Limitations: Strengths include the large, international, randomized design, the use of a placebo control, and long-term follow-up. Limitations include the inability to isolate the effects of neoadjuvant versus adjuvant pembrolizumab and the exclusion of adjuvant capecitabine from the treatment protocol.
Future Research: Further studies should focus on identifying biomarkers predictive of response to pembrolizumab, optimizing the sequencing and duration of immunotherapy, and evaluating the addition of other agents to improve outcomes in early-stage TNBC.
Meta-Analysis: Moderate Hypofractionation Improves Safety and Cosmesis Over Conventional Fractionation in Breast Cancer Radiotherapy
17 Sep, 2024 | 11:14h | UTCBackground:
Breast cancer remains the most prevalent malignancy among women worldwide, with postoperative radiation therapy playing a crucial role in reducing locoregional recurrence and improving survival outcomes. Conventional fractionation (CF), involving a total dose of approximately 50 Gy delivered over five to six weeks in daily fractions of 1.8–2 Gy, has been the historical standard. In recent years, hypofractionated regimens—including moderate hypofractionation (MHF) and ultra-hypofractionation (UHF)—have emerged as alternatives that offer shorter treatment durations. Despite evidence supporting hypofractionation, its adoption varies due to concerns about potential side effects, cosmetic outcomes, and the limited long-term data on UHF.
Objective:
To provide a comprehensive assessment of various radiation dose fractionation schemes—CF, MHF, and UHF—in breast cancer, focusing on side effects, cosmesis, quality of life, recurrence risks, and survival outcomes.
Methods:
A systematic review and meta-analysis were conducted by searching Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 October 2023. Randomized controlled trials comparing CF (daily fractions of 1.8–2 Gy over 5–6 weeks), MHF (fractions of 2.65–3.3 Gy over 3–5 weeks), and UHF (five fractions) were included. Two independent investigators screened studies, extracted data, and assessed risk of bias using the Cochrane Collaboration’s tool and the GRADE approach. Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. A network meta-analysis integrated all available evidence.
Results:
From 1,754 studies, 35 trials encompassing 20,237 patients were included. Compared with CF, MHF significantly reduced the risk of grade ≥2 acute radiation dermatitis:
- All patients: RR, 0.59; 95% CI, 0.51–0.69; P<0.001.
- Breast-Conserving Therapy: RR, 0.54; 95% CI, 0.49–0.61; P<0.001.
- Post-Mastectomy: RR, 0.68; 95% CI, 0.49–0.93; P=0.02.
MHF also showed lower incidences of:
- Hyperpigmentation: RR, 0.77; 95% CI, 0.62–0.95; P=0.02.
- Grade ≥2 Breast Shrinkage: RR, 0.92; 95% CI, 0.85–0.99; P=0.03.
MHF was associated with improved cosmesis and quality of life compared to CF. Survival and recurrence outcomes were similar across UHF, MHF, and CF regimens. While UHF demonstrated comparable safety and efficacy profiles, data were less conclusive due to fewer trials and shorter follow-up periods.
Conclusions:
Moderate hypofractionation improves safety profiles, cosmetic outcomes, and quality of life compared with conventional fractionation while maintaining equivalent oncological efficacy. Ultra-hypofractionation shows promise with similar short-term safety and effectiveness but requires further research for definitive conclusions.
Implications for Practice:
- Preferred Regimen: MHF should be considered the preferred radiation therapy regimen for breast cancer patients due to reduced side effects, improved cosmesis, shorter treatment duration, and maintained oncological outcomes.
- Ultra-Hypofractionation Potential: UHF offers advantages of further reduced treatment times and patient convenience but requires additional long-term data before widespread adoption.
- Resource Utilization: Adoption of hypofractionated regimens can improve healthcare resource utilization and enhance patient quality of life.
Study Strengths and Limitations:
Strengths include a comprehensive assessment of both clinical and patient-centered outcomes across a large number of randomized controlled trials, providing a multidimensional perspective crucial for informed clinical decision-making.
Limitations involve potential risk of bias due to lack of blinding in some studies, variability in outcome reporting across trials, and limited long-term data on UHF regimens.
Future Research:
Further studies are needed to solidify the evidence base for UHF, particularly regarding long-term safety and efficacy. Research should focus on optimizing fractionation regimens tailored to patient-specific factors, such as breast size and smoking status, to enhance outcomes.
Reference:
RCT: Omission of axillary dissection noninferior to complete dissection in clinically node-negative breast cancer with sentinel-node metastases – N Engl J Med
25 May, 2024 | 18:57h | UTCStudy Design and Population: This noninferiority trial explored the effects of omitting completion axillary-lymph-node dissection in patients with clinically node-negative primary T1 to T3 breast cancer who had one or two sentinel-node macrometastases. A total of 2766 patients were enrolled and randomized 1:1 to either undergo sentinel-node biopsy only or completion dissection. Patients received adjuvant treatment and radiation therapy as per national guidelines, focusing on recurrence-free survival as a secondary end point.
Main Findings: The study reported that the 5-year recurrence-free survival rates were 89.7% in the sentinel-node biopsy-only group and 88.7% in the dissection group, with a country-adjusted hazard ratio for recurrence or death at 0.89 (95% CI, 0.66 to 1.19), significantly below the noninferiority margin (P<0.001). This outcome demonstrates the noninferiority of the less invasive sentinel-node biopsy approach compared to the traditional dissection method in managing sentinel-node macrometastases.
Implications for Practice: The findings suggest that for clinically node-negative breast cancer patients with sentinel-node macrometastases, omitting axillary-lymph-node dissection could be considered a viable treatment option, potentially reducing the surgical burden without compromising recurrence-free survival outcomes. This could lead to adjustments in surgical practice and patient care strategies, emphasizing a less invasive approach while maintaining clinical efficacy.
Reference (link to abstract – $ for full-text):
USPSTF Guideline: Biennial screening mammography recommended for women aged 40-74 to reduce breast cancer morbidity and mortality
1 May, 2024 | 21:45h | UTCStudy Design and Population:
The US Preventive Services Task Force (USPSTF) performed a systematic review and collaborated on modeling studies to evaluate the effectiveness of various mammography-based breast cancer screening strategies. This assessment included factors such as age of initiation and cessation of screening, screening intervals, modalities, and the use of supplemental imaging. The population studied consisted of cisgender women and all other persons assigned female at birth who are 40 years or older and at average risk of breast cancer.
Main Findings:
The USPSTF concludes with moderate certainty that biennial screening mammography for women aged 40 to 74 years provides a moderate net benefit in reducing the incidence of and progression to advanced breast cancer, as well as in decreasing breast cancer morbidity and mortality. However, the evidence is insufficient to assess the benefits and harms of mammography screening in women aged 75 and older, as well as the use of supplemental screening with ultrasound or MRI in women with dense breasts.
Implications for Practice:
Based on these findings, the USPSTF recommends biennial screening mammography for women aged 40 to 74 years. This recommendation aims to optimize breast cancer outcomes while considering the balance of benefits and harms of screening. There is a need for further research to clarify the benefits and risks associated with mammography in women older than 75 and for those with dense breasts considering supplemental screening.
Commentary on X (thread – click for more)
???? Just published: USPSTF recommends all women undergo routine #breastcancer screening every other year beginning at age 40, an update from the 2016 recommendation to start at age 50.
https://t.co/xDPK4qu7JH pic.twitter.com/3zVBMWeuKb— JAMA (@JAMA_current) April 30, 2024
Reference (link to free full-text):
RCT: Aspirin fails to improve invasive disease-free survival in breast cancer patients
1 May, 2024 | 21:37h | UTCThis randomized clinical trial assessed the efficacy of daily aspirin (300 mg) as adjuvant therapy in reducing breast cancer recurrence among 3020 participants with high-risk nonmetastatic breast cancer across the United States and Canada. The study, which followed participants for a median of 33.8 months, found no significant benefit of aspirin on invasive disease-free survival or overall survival, with the hazard ratio for disease-free survival being 1.27 (95% CI, 0.99-1.63; P = .06) and for overall survival 1.19 (95% CI, 0.82-1.72). Given these findings, aspirin is not recommended as an adjuvant treatment for breast cancer, challenging earlier observational data that suggested a potential survival benefit in breast cancer survivors. The trial was concluded early due to the lack of observed benefits, with adverse event rates being similar in both the aspirin and placebo groups.
Commentary on X:
Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. https://t.co/uPWTeaqXdJ pic.twitter.com/x6Qb4bRlqF
— JAMA (@JAMA_current) April 29, 2024
Reference (link to abstract – $ for full-text):
RCT | Mammography screening with AI reduces workload by 44.3% without loss in detection efficacy
4 Aug, 2023 | 12:13h | UTCArtificial intelligence-supported screen reading versus standard double reading in the Mammography Screening with Artificial Intelligence trial (MASAI): a clinical safety analysis of a randomised, controlled, non-inferiority, single-blinded, screening accuracy study – The Lancet Oncology (link to abstract – $ for full-text)
News Release: First randomized trial finds AI-supported mammography screening is safe and almost halves radiologist workload – Lancet
Commentaries:
Large Mammography Study Shows Significant Benefits with AI-Aided Screening – Diagnostic Imaging
Review | Atypical hyperplasia of the breast: Clinical cases and management strategies
3 Aug, 2023 | 13:07h | UTC
Systematic Review | Post-mastectomy RT likely lowers recurrence and improves survival in early breast cancer with 1-3 positive nodes
25 Jul, 2023 | 13:34h | UTC
Changes to breast structure and function across a woman’s lifespan: implications for managing and modeling female breast injuries
19 Jul, 2023 | 14:29h | UTC
RCT | Total breast reconstruction with autologous fat transfer using an expansion device vs implants in patients with breast cancer
28 Jun, 2023 | 13:12h | UTCEffect of Total Breast Reconstruction With Autologous Fat Transfer Using an Expansion Device vs Implants on Quality of Life Among Patients With Breast Cancer: A Randomized Clinical Trial – JAMA Surgery (link to abstract – $ for full-text)
See also: Visual Abstract
Author Interview: Effect of Breast Reconstruction With Autologous Fat Transfer vs Implants on Quality of Life – JAMA
M-A | Effectiveness of physical therapy in axillary web syndrome after breast cancer
27 Jun, 2023 | 13:28h | UTC
Cohort Study | Steady reduction in breast cancer mortality from 1993-2015 in England
22 Jun, 2023 | 14:58h | UTCInvited Commentary: Risk of breast cancer death after a diagnosis of early invasive breast cancer – The BMJ
Commentary on Twitter
NEW research finds that most women diagnosed with early breast cancer can expect to become long term cancer survivors https://t.co/TaYqRJD6Lu pic.twitter.com/V15bLdmI2H
— The BMJ (@bmj_latest) June 14, 2023
Updated Guidance | Diagnosis and treatment of Early and locally advanced breast cancer
22 Jun, 2023 | 14:52h | UTC
RCT | Increased detection of metastases via PET-CT alters treatment path in locally advanced breast cancer
16 Jun, 2023 | 14:02h | UTCImpact of 18F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer – Journal of Clinical Oncology (link to abstract – $ for full-text)
ASCO Guideline Update | Human epidermal growth factor receptor 2 testing in breast cancer
14 Jun, 2023 | 14:15h | UTC
Review | Inflammatory lesions of the breast
2 Jun, 2023 | 12:10h | UTCInflammatory Lesions of the Breast – Archives of Pathology and Laboratory Medicine
Review | Managing menopausal symptoms, fertility, and bone health in breast cancer women on endocrine therapy
30 May, 2023 | 11:40h | UTC
USPSTF Draft Statement recommends biennial screening mammography for women ages 40 to 74 years
22 May, 2023 | 13:56h | UTCBreast Cancer: Screening – U.S. Preventive Services Task Force
Critical perspectives on the statement:
Earlier screening for breast cancer: Benefits and harms – Lown Institute
Why more mammograms aren’t the solution to breast cancer – Vox
Cohort Study | Following lifestyle recommendations linked to lower recurrence in high-risk breast cancer
15 May, 2023 | 12:48h | UTCCommentary: Adherence to healthy lifestyle found to cut breast cancer recurrence, mortality – HealthDay
Commentary on Twitter
Adherence to the @AmericanCancer and the @aicrtweets lifestyle recommendations before and after high-risk breast cancer treatment was associated with a 37% reduced risk of disease recurrence and a 58% reduction in mortality. https://t.co/sy6b8CGgr1
— JAMA Network Open (@JAMANetworkOpen) May 4, 2023
Uncertainties and controversies in axillary management of patients with breast cancer
11 May, 2023 | 11:53h | UTC
Single-arm study | Halting endocrine therapy for pregnancy not linked to increased breast cancer events vs. a control cohort
10 May, 2023 | 16:01h | UTCInterrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
In women with previous breast cancer who temporarily discontinued adjuvant endocrine therapy to attempt pregnancy, the frequency of breast cancer events was below the prespecified safety threshold and similar to that in controls (POSITIVE trial). https://t.co/zM3f4SbgjE
— NEJM (@NEJM) May 3, 2023
New ACR breast cancer screening guidelines call for earlier and more-intensive screening for high-risk women
9 May, 2023 | 14:50h | UTCGuideline: Breast Cancer Screening for Women at Higher-than-Average Risk: Updated Recommendations from the ACR
Effects of intraoperative fluorescence guidance for breast cancer lumpectomy surgery
9 May, 2023 | 14:48h | UTCIntraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery – NEJM Evidence
News Release: Study finds fluorescent guide can help detect tumor left behind after breast cancer surgery – Mass General Brigham
M-A | Quality of life after risk-reducing surgery for breast and ovarian cancer prevention
9 May, 2023 | 14:21h | UTC