Clinical breast cancer最新文献

Introduction: The role of postmastectomy radiotherapy (PMRT) in clinical prognostic stage I-III breast cancer patients with positive responses and achieving ypN0 after Neoadjuvant therapy (NAT) is controversial.

Methods: 3557 patients with TNM clinical prognostic stage (AJCC 8th Edition) I-III breast cancer with positive responses and achieving ypN0 following neoadjuvant therapy were selected from the Surveillance, Epidemiology, and End Results (SEER) database and followed through the end of 2020. COX proportional hazards models were employed to examine the associations between clinical or pathological parameters and OS. Propensity score matching (PSM) was employed to control for confounding variables and multiple association inference models were used for progressive sensitivity analysis.

Results: In the multivariate analysis, PMRT did not demonstrate a significant improvement in OS (P = .127), while in univariate analysis, it was linked to worse OS (P < .001). PSM and multiple association inference models indicated that PMRT did not confer any significant improvement in patients' OS (all P > .05). Further stratified analysis of the prematch subgroup revealed that PMRT was linked to the 68% lower risk of mortality in patients with the cN3 subgroup (HR: 0.32; 95%CI, 0.11-0.97), and expressly enhanced the OS in cN3 subgroup patients with ER-, PR-, HER-2- status, and PR to NAT.

Conclusions: Our research indicated that PMRT did not show any survival benefits for clinical prognostic stage I-III breast cancer patients who had positive responses and achieved ypN0 after NAT. PMRT was linked to the reduction in mortality among patients in the cN3 subgroup.

This review aims to investigate the issue of treatment nonadherence and to present the available strategies to improve adherence to oral treatments in breast cancer. A literature search was conducted to contextualise the issue of nonadherence, investigate the reasons behind nonadherence, and demonstrate strategies to address treatment nonadherence in breast cancer. Findings indicate that adherence rates decrease while discontinuation rates increase with increasing lengths of breast cancer treatment course. Lack of adherence is proven to be detrimental to treatment outcomes. Patients struggle to adhere to treatment due to inadequate relationships with healthcare providers, lack of information, psychological distress, and side effects. Healthcare providers should evaluate patient's experience to provide the necessary support. Following this assessment, healthcare providers may recommend interventions addressing patient knowledge, psychological distress or side effects. Treatment adherence remains an issue for oral therapeutics in breast cancer. After patient assessment, healthcare providers can offer personalised strategies to improve treatment adherence. The most crucial interventions address patient knowledge, psychological distress, and side effects.

Background: Lasofoxifene, a novel endocrine therapy (ET), showed antitumor activity versus fulvestrant in women with ESR1-mutated, metastatic breast cancer (mBC) that progressed on prior ET (phase 2, ELAINE 1 study). We investigated changes in genitourinary syndrome of menopause (GSM) vulvar-vaginal symptoms with lasofoxifene and how patient/disease characteristics affect baseline vulvar-vaginal symptoms in ELAINE 1.

Methods: Women were randomized to oral lasofoxifene 5 mg/day or IM fulvestrant 500 mg (days 1, 15, and 29, then every 28 days) until disease progression/severe toxicity. Changes in mean vaginal (VAS) and vulvar (VuAS) assessment scales, and their composite (average of all symptom scores/patient), from baseline to week 16, and mean baseline VAS/VuAS scores by patient/disease characteristics, were descriptively summarized.

Results: Of 103 enrolled patients, 72 (70%) completed the VAS/VuAS (mean age 61.5 years). Vaginal (40%)/vulvar (25%) dryness and vaginal pain (22%) were the most frequently reported symptoms; 26% reported ≥1 moderate/severe symptom. Lasofoxifene decreased the mean composite VAS/VuAS, VAS, and VuAS from baseline to week 16 by 74%, 74%, and 79%, respectively; fulvestrant increased them by 36%, 15%, and 63%, respectively. Baseline vaginal/vulvar symptoms were more severe if patients were under age 40, had no visceral disease, used adjuvant tamoxifen previously, or had longer AI duration in the adjuvant/metastatic settings.

Conclusions: Oral lasofoxifene (5 mg/day), but not fulvestrant, appears to improve GSM vaginal symptoms in women with mBC. These preliminary findings suggest further study is needed; such will be explored in the phase 3, registrational, ELAINE 3 trial in patients with ESR1-mutated, ER+/HER2- mBC.

Breast cancer (BC) now holds the top position as the primary reason of cancer-related fatalities worldwide, overtaking lung cancer. BC is classified into diverse categories depending on histopathological type, hormone receptor status, and gene expression profile, with ongoing evolution in their classifications. Cancer initiates and advances when there is a disruption in cell death pathways. In BC, the primary cell death pathway, apoptosis, experiences dysregulation across multiple stages. Ongoing studies aim to discover therapeutic targets that enhance cancer cell susceptibility to apoptosis. However, resistance to this therapy remains a significant challenge in treating BC. If apoptosis is hindered, investigating alternative pathways for cell death that can effectively eradicate BC cells during treatment becomes a valuable endeavor. In this context, necroptosis is gaining considerable focus as an alternative cell death pathway. Necroptosis represents a programmed version of necrosis which shares its key regulators with apoptosis. When apoptosis is hampered, necroptosis serves as an alternative cell death pathway even in physiological conditions like formation of limbs during embryonic development. Additionally, it comes into play during bacterial and viral infections when the apoptosis machinery is hijacked and inhibited by proteins from these pathogens. Studies reveal that in BC, mutations significantly impact molecules in the apoptosis pathway, contributing to the onset, advancement, and multiplication of cancer cells. Although some studies do indicate that the functionality of necroptosis pathway may be compromised in malignancy the status of its key molecules remains largely unknown. In this article, we aim to gather the known mutations present in key molecules of necroptosis among various subtypes of BC, utilizing data from the Cosmic and UniProt databases. The same may help to enhance the development of therapeutic strategies to effectively induce necroptosis in apoptosis-resistant BCs.

Background: The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone, in combination with fulvestrant as second-line therapy for patients with ER+, PgR+/-, HER2- metastatic breast cancer. This study was terminated early and herein, we report patient characteristics, and outcomes.

Methods: Eligibility criteria included disease progression on ≥2 lines of prior therapy, ECOG performance status ≤ 2, measurable disease per RECIST 1.1 criteria, and optional ¹⁸F-fluorofuranylnorprogesterone (¹⁸F-FFNP) PET/CT imaging.

Results: Consented subjects received standard-dose fulvestrant plus onapristone 50 mg orally, twice daily, until disease progression, or unacceptable toxicity. The study enrolled 11 women from 2 sites within the Wisconsin Oncology Network from November 2021 through March 2023. Mean age of the subjects was 58.5 years. Other than grade 1 toxicities, the treatment was well tolerated. None of the 11 subjects met RECIST 1.1 definition of response. The median time to progression was 63 days. A total of 4 of 11 patients had stable disease as best response and 2 of them were on treatment for 5.5 and 7.7 months. Two of the 11 subjects underwent functional imaging with ¹⁸F-FFNP PET/CT before and 10 or 14 days after starting treatment. For both subjects, tumor uptake of ¹⁸F-FFNP was stable or increased in all target lesions while ¹⁸F-FFNP uptake in the uterus, a normal PgR-rich internal control organ, was decreased.

Conclusion: The study regimen was well-tolerated with no significant toxicities. Future studies may evaluate antiprogestins with various combinations such as targeted therapies.

Background: The use of the residual cancer burden (RCB) for assessing breast cancer after neoadjuvant therapy (NAT) is increasingly common, but the prognostic difference between RCB 0 and RCB I is unclear.

Methods: We systematically reviewed literature from PubMed, Embase, Web of Science, and oncology conferences until September 24, 2023. We used fixed- and random-effects models to calculate hazard ratio (HR) with 95% confidence interval (CI) for event-free survival (EFS), overall survival (OS), and distant disease-free survival (DDFS).

Results: Our meta-analysis, encompassing 19 studies with 5894 patients, revealed that in the general population, RCB I had worse EFS (HR = 2.13; 95% CI: 1.75-2.58), OS (HR = 2.08; 95% CI: 1.48-2.93), and DDFS (HR = 2.10; 95% CI: 1.65-2.67) than RCB 0. Consistent with results from the general population, RCB I exhibited poorer EFS, OS, and DDFS in human epidermal growth factor 2-positive (HER2+) subtype and triple-negative breast cancer (TNBC) compared to RCB 0. Conversely, luminal subtype with RCB 0 and RCB I showed similar EFS (HR = 1.04; 95% CI: 0.62-1.72).

Conclusions: RCB I experienced a poorer prognosis compared to RCB 0 in the general population, a pattern also observed in the HER2+ subtype and TNBC. However, no significant prognostic disparity was noted between RCB 0 and RCB I in the luminal subtype.

Aim: To compare menopausal symptoms between tamoxifen alone and tamoxifen with ovarian function suppression (OFS) over 12 months, identifying related factors.

Methods: This prospective, observational study included 209 premenopausal patients with breast cancer on tamoxifen, recruited from Asan Medical Center, Republic of Korea. We collected demographic and clinical information from the participants' medical records and assessed menopausal symptoms using the Korean Menopause Rating Scale (MRS) at 3-, 6-, and 12-months postdiagnosis.

Results: Of the 209 participants, 27.8% were administered tamoxifen in conjunction with OFS. Compared with the tamoxifen alone group, the tamoxifen plus OFS group had lower baseline MRS scores but higher scores at 6 and 12 months, and the scores showed a plateau within a year for both groups. Factors contributing to higher MRS scores at 6 months included the baseline MRS score (estimate, -0.326; standard error, 0.077) and addition of OFS (estimate, 6.084; standard error, 1.306; P < .001 for both). A significant interaction between OFS and prior chemotherapy was identified, with the OFS impact being significantly notable only in patients without prior chemotherapy (estimate, -6.643; standard error, 2.946; P = .025).

Conclusions: Addition of OFS to tamoxifen in premenopausal patients with breast cancer can exacerbate menopausal symptoms relative to those when tamoxifen is used alone, especially in patients without prior chemotherapy. Thus, personalized treatment decisions about ovarian function suppression should consider potential symptom burdens, particularly for chemotherapy-naive patients, to balance treatment efficacy and quality of life.

Background: Adjuvant therapy decisions in hormone receptor positive, HER2 negative breast cancer are evolving. Gene panel testing has reduced the number of patients recommended for chemotherapy by up to two thirds. Identifying low risk genomic cases before testing could represent a significant economic impact. Systemic inflammatory indices have shown promise as prognostic markers in early breast cancer. We investigated the utility of four systemic inflammatory indices with the Nottingham Prognostic Index to predict the Oncotype DX® recurrence scores threshold level (low or high score), in women aged 50 and over with node negative invasive ductal carcinoma of the breast.

Methods: A retrospective review of 245 patients with Oncotype DX® Recurrence Score testing from 2007 to 2021 were identified. The Nottingham Prognostic Index and systemic inflammatory indices ratios were estimated from histology results and preoperative peripheral blood samples respectively.

Results: 22.4% of the cohort had a Recurrence Score in the higher risk group. This group had a greater percentage of grade 3 tumours, progesterone receptor negativity, higher Nottingham Prognostic Scores, and inflammatory indices ratios than the lower risk group. A decision tree incorporating the Neutrophil Lymphocyte Ratio with clinicopathological features showed potential as an indicator of a high Oncotype DX® RS score, such that further investigation is warranted to assess whether Recurrence Score testing could be triaged in certain cohorts of patients. In this study, 38% of patients might be able to avoid genomic testing based on the decision tree analysis.

Conclusion: Utility of inflammatory indices with clinicopathological features may help triage gene panel testing.

Introduction: Adjuvant abemaciclib was recently approved in high-risk early breast cancer, leading to an increase in oncology resource utilisation. We thus developed a regional, remote monitoring clinical service. The set-up, delivery processes and outcomes from the first 6 months' consecutive patients are presented.

Methods: A regional delivery model with remote monitoring using optional electronic patient outcome measures (ePROMs) and bloods closer to home (BCTH) was implemented. Electronic patient records of patients entering the service (October 31, 2022 to May 31, 2023) were reviewed. Time-in-motion and on-line patient satisfaction surveys were conducted with questions adapted from prior questionnaires used by our cancer center. An independent t-test was used to assess differences in creatinine levels whilst on abemaciclib and a Mann-Whitney test to determine whether the time taken to complete follow-up appointments differed with and without ePROMs.

Results: The first 103 patients to commence abemaciclib (median age 58 [range, 27-85], 66.0% White) had completed a median of 6 cycles (range, 0-9). 51.5% had treatment interruption, 52.4% a dose reduction and 15.5% discontinued therapy. Diarrhoea (90.3%), fatigue (84.9%) and anorexia (73.1%) were the most commonly reported toxicities on ePROMs. 10.8% of patients reported grade 3-4 toxicities. Neutropenia was also common and low grade. 89.5% of patients would recommend ePROMs and 98.0% found the BCTH service easy to use. Review appointments with ePROMs were a similar length to those without (P = .138).

Conclusions: We have successfully implemented a remote, regional adjuvant clinical service which could serve as a blueprint for other NHS trusts for this and other cancer drugs.

Purpose: To validate the Axillary Reverse Mapping (ARM) technique with indocyanine green (ICG), focusing on the detection rate and the procedure's feasibility. The predictive factors for metastatic involvement of ARM nodes are also analyzed to define the target population for ARM indication.

Methods: This prospective, observational, non-randomized study of patients with breast cancer included patients with an indication for axillary lymph node dissection (ALND) performed between June 2021 and June 2023. Participants were divided into two cohorts based on pattern of ICG migration: standard technique (all ARM nodes) and targeted technique (in contact with axillary vein). The feasibility of identifying and preserving ARM nodes during ALND was assessed. Multivariate logistic regression was used to analyze predictive factors (eg, tumor size, molecular surrogate subtype, multifocality, and neoadjuvant therapy) for metastatic ARM nodes.

Results: Of the 41 patients in whom we performed the ARM technique, ARM nodes were identified and preserved after ALND in 36 patients (87.8%). Of these, 17 (89.5%) underwent the standard technique and 19 (86.4%) underwent the targeted technique. ARM metastases were identified in 12 patients: 9 (47.1%) with the standard technique and 3 (15.7%) with the targeted technique (P = .026). The ARM technique was the only risk factor for ARM involvement (odds ratio, 15.9; 95% confidence interval, 1.1-218.6).

Conclusions: ICG facilitates the successful completion of ARM in almost 90% of patients undergoing ALND. In addition, by selecting the ARM nodes closest to the axillary vein, the number of cross metastases can be significantly reduced.