Adjuvant Endocrine Therapy Research Articles

New therapies for hormone-positive HER2-negative metastatic breast cancer with AKT signaling alterations: the Expert Panel Decision

On May 20, 2024, the Expert Panel discussed key issues of the diagnosis of alterations of the AKT signaling pathway, the effectiveness and safety of targeted therapy for hormone-positive (HR+) HER2-negative metastatic breast cancer (BC) concerning the emergence of a new selective AKT inhibitor capivasertib. The results of the CAPItello-291 study are presented. The experts concluded that a new effective treatment line has become available for patients with hormone-resistant advanced hormone-positive HER2-negative BC with genetic alterations in the AKT signaling pathway and relapse on previous adjuvant endocrine therapy with aromatase inhibitors or within the first year after the therapy or with progression during previous therapy with aromatase inhibitors for metastatic BC. Modern genetic testing methods for the alterations in the AKT signaling pathway can confirm the presence of this key biological target in the tumor for tailoring effective targeted therapy.

Systemic hormone therapy after breast and gynecological cancers: an Italian expert group consensus opinion.

The specific Italian Group of Study of the Menopause formulated a consensus opinion on the use of estrogen therapy (ET) or combined estro-progestin hormone therapy (HT) after breast and gynecological cancers. This consensus is based on the risk of recurrence of the specific cancer during ET/HT, the presence of steroid receptors in cancer cells, the use of adjuvant hormone therapies and data on the use of ET/HT after cancer. The following positions were reached. ET/HT can be used after vulvar cancers and melanoma, but with great caution after the rare adenocarcinomas. ET/HT can be used after cervical cancer, but ET should be used with caution after adenocarcinomas. ET/HT can be used after International Federation of Obstetrics and Gynecology (FIGO) stage I-II estrogen-dependent endometrial cancers, except in Black women, and can probably be used after estrogen-independent endometrial cancers. ET/HT cannot be administered or should be used with great caution after most uterine sarcomas. ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer.

The impact of high exposure to perfluoroalkyl substances and risk for hormone receptor-positive breast cancer – A Swedish cohort study

IntroductionPerfluoroalkyl substances (PFAS) are persisting chemicals with endocrine disruptive and carcinogenic properties. Previous studies involving cohorts with high PFAS exposure have not shown an increased risk of breast cancer. Research on PFAS and breast cancer according to hormone receptor status is limited. This study aims to investigate the association between PFAS exposure and hormone receptor-positive breast cancer. Materials and MethodsIn 2013, high levels of PFAS (sum of PFAS > 10,000 ng/L), dominated by perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) were found in the drinking water from one of the two waterworks in Ronneby, Sweden. Breast cancer diagnoses and information of adjuvant endocrine therapy were retrieved from the Swedish Cancer Register and The Prescribed Drug Register 2006–2016 for a cohort of women residing in the municipality between 1985 and 2013 (n = 24,509). Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential addresses. Cox proportional hazards models were used in the analysis. The highest achieved educational level was used as an indicator of socioeconomic position. Sensitivity and subgroup analysis were performed for prepubertal exposure and diagnosis before or after age 50 (assumed menopause). ResultsThere were 313 cases of malignant breast cancer among women ≤ 85 years between 2006 and 2016. Of these, 224 cases (72 %) were considered hormone receptor-positive based on the first prescription of adjuvant endocrine therapy, antiestrogens (40 %) or aromatase inhibitor (60 %). Among women ever living at a residential address with high PFAS exposure, the hazard ratio (HR) for breast cancer classified as hormone receptor-positive was 0.84; 95 % confidence interval (CI) 0.61, 1.14. Findings were similar before and after menopause. ConclusionHigh PFAS exposure from drinking water, dominated by PFOS and PFHxS, was not associated with an elevated risk of hormone receptor-positive breast cancer.

Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer

BackgroundInavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex (encoded by PIK3CA) that also promotes the degradation of mutated p110α. Inavolisib plus palbociclib–fulvestrant has shown synergistic activity in preclinical models and promising antitumor activity in early-phase trials.MethodsIn a phase 3, double-blind, randomized trial, we compared first-line inavolisib (at an oral dose of 9 mg once daily) plus palbociclib–fulvestrant (inavolisib group) with placebo plus palbociclib–fulvestrant (placebo group) in patients with PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after the completion of adjuvant endocrine therapy. The primary end point was progression-free survival as assessed by the investigator.ResultsA total of 161 patients were assigned to the inavolisib group and 164 to the placebo group; the median follow-up was 21.3 months and 21.5 months, respectively. The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI, 5.6 to 9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32 to 0.59; P<0.001). An objective response occurred in 58.4% of the patients in the inavolisib group and in 25.0% of those in the placebo group. The incidence of grade 3 or 4 neutropenia was 80.2% in the inavolisib group and 78.4% in the placebo group; grade 3 or 4 hyperglycemia, 5.6% and 0%, respectively; grade 3 or 4 stomatitis or mucosal inflammation, 5.6% and 0%; and grade 3 or 4 diarrhea, 3.7% and 0%. No grade 3 or 4 rash was observed. Discontinuation of any trial agent because of adverse events occurred in 6.8% of the patients in the inavolisib group and in 0.6% of those in the placebo group.ConclusionsIn patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib–fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib–fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann–La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.)

Advances in Treatment for Oestrogen Receptor-Positive Breast Cancer

THIS YEAR the European Society for Medical Oncology (ESMO) Congress was hosted in Barcelona, Spain from 13th–17th September. Among the many impactful sessions, a symposium titled ‘Incorporating Novel Treatment Insights for Estrogen Receptor-Positive (ER+) Early Breast Cancer Patients’ garnered particular attention. Featuring presentations by Stephen Johnston, Royal Marsden, London, UK; Nadia Harbeck, Ludwig Maximilian University of Munich, Germany; and Etienne Brain, Institut Curie in Paris &amp; Saint-Cloud, France, the session provided a comprehensive overview of current advances in ER+ early breast cancer treatment. The speakers explored adjuvant endocrine therapies, prognostic and predictive factors for clinical decision-making, and the unique challenges of optimising treatment for older patients, underscoring the evolving landscape of personalised care in ER+ early breast cancer.

Risk of type-2-diabetes after breast cancer treatment: a population-based cohort study in Denmark.

Data on type 2 diabetes (T2D) risk after breast cancer (BC) could guide preventive strategies. Yet, studies had limitations regarding sample size, follow-up, and contemporary treatments. We evaluated the risk of T2D after BC overall, by cancer treatment, and compared with a matched cohort of cancer-free women. We assembled a population-based cohort of early-stage BC patients aged ≥30 years diagnosed during 1996-2021 in Denmark. We created a comparison cohort of five cancer- and T2D-free women for each BC case, matched six months after BC diagnosis date on age and region. We followed both cohorts until T2D diagnosis, emigration, death, or December 31, 2022. We computed 5-year cumulative incidences and used Cox models to calculate time-varying adjusted hazard ratios (aHR) of T2D. Among 74,526 BC survivors and 372,630 matched cancer-free women, 5-year cumulative incidences of T2D were 3.8% (95%CI = 3.7-3.9) and 3.3% (95%CI = 3.3-3.4), respectively. The aHR of T2D was elevated but attenuated over follow-up (aHR5-years=1.20, 95%CI = 1.15-1.25, and aHR15-years=1.09, 95%CI = 1.05-1.12). Adjuvant endocrine therapy (aHR = 1.14; 95%CI = 1.10-1.19), aromatase inhibitors (aHR = 1.25; 95%CI = 1.18-1.32), and less so tamoxifen (aHR = 1.05; 95%CI = 0.99-1.11), were associated with elevated risk of T2D in women with BC vs cancer-free women. Among BC patients, chemotherapy (aHR = 1.10, 95%CI = 1.03-1.17) and radiation therapy (right-sided aHR = 1.18, 95%CI = 1.09-1.27 and left-sided aHR = 1.24, 95%CI = 1.15-1.33) were associated with increased T2D risk. BC was associated with excess risk of T2D, though of lower magnitude than previously reported. The excess risk was temporary and related to BC treatment but could also be influenced by obesity and heightened T2D diagnostic activity.

Comparing Black and White Patients in Treatment of Advanced Prostate Cancer and Survival in an Equal Access Health System.

Racial disparities in prostate cancer treatment and survival in the U.S. have been attributed to differences in access to care and medical insurance. We aimed to compare treatment and survival of advanced prostate cancers between White and Black men in the equal access Military Health System (MHS). We accessed the MilCanEpi database to study a cohort of non-Hispanic White and Black men diagnosed with stage III or IV prostate cancer between 1998 and 2014 in the MHS. The racial groups were compared in receiving curative treatment of radical prostatectomy (RP) only, RP with (neo)adjuvant radiation or hormone therapy, radiation only, or combination radiation and hormone therapy; and overall survival using multivariable regression models. The study included 1476 White and 531 Black men. Overall, there was no racial difference in receiving any curative treatment (AOR = 0.85, 95% CI = 0.67, 1.08 for Black vs. White). By treatment type, Black men were statistically as likely to receive RP only (AOR = 0.87, 95% CI = 0.67, 1.14), radiation only (AOR = 0.81, 95% CI = 0.49, 1.34), or combination radiation and hormone therapy (AOR = 1.12, 95% CI = 0.71, 1.78) but statistically less likely to receive RP with (neo)adjuvant treatment (AOR = 0.56, 95% CI = 0.37, 0.86) relative to no curative treatment compared to White men. The difference in RP with (neo)adjuvant treatment was also statistically significant among patients with stage III tumors, but not stage IV. Survival was similar overall (AHR = 1.12, 95% CI = 0.88, 1.42 for Black vs. White) and when evaluated by tumor stage. In the MHS, the overall likelihood to receive any treatment for advanced prostate cancers and survival was similar between races, which might result from universal health care. Racial differences in receipt of RP with (neo)adjuvant treatment, especially for patients with stage III prostate cancer, may be related to factors other than access to care and warrants further research.

Impact of extended endocrine therapy for patients with risk factors for late recurrence in estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer after 5years of endocrine therapy.

Extended endocrine therapy shows promise for reducing the recurrence of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, its benefits in patients with high-risk factors for late recurrence remain unclear, particularly in premenopausal patients. In this study, we aimed to explore the impact of extended endocrine therapy in patients with risk factors for late recurrence of postmenopausal and premenopausal ER-positive, HER2-negative breast cancer. We retrospectively analyzed data from patients with ER-positive, HER2-negative breast cancer at Tohoku Kosai Hospital who were disease-free after 5years of adjuvant endocrine therapy. The patients were classified as high risk based on lymph node positivity, tumor size > 2cm, or high tumor grade. The high-risk group was further divided into extended therapy and stop groups. Propensity score matching was applied to balance baseline characteristics. Disease-free survival (DFS) was the primary endpoint. Among the 1474 eligible patients, 224 received extended endocrine therapy, and 1250 stopped therapy. After propensity score matching, the high-risk group comprised 348 patients (n = 174 patients/group). The extended therapy group had significantly higher 10-year DFS and distant DFS rates than the stop group. The multivariate Cox model indicated a 69% reduction in recurrence risk in the extended therapy group. Extended endocrine therapy can substantially improve DFS in patients with high-risk ER-positive, HER2-negative breast cancer, especially in those with large tumors, lymph node involvement, and high tumor grade. These findings support personalized treatment strategies for enhancing long-term outcomes.

"It Is What It Is" - The Lived Experience of Women With Breast Cancer Undergoing Axillary Lymph Node Dissection.

The lived experience of women undergoing axillary procedures as part of their breast cancer (BC) treatment remains unexplored. This lack of in-depth understanding could hamper implementation of person-centred care, which is concerning because BC is the most common form of cancer in women. The aim of this study was therefore to explore the lived experiences of women undergoing axillary lymph node dissection (ALND) due to BC. Twelve women with a mean age of 59 years were interviewed about their lived experiences of axillary procedures as part of their BC treatment. The interviews were recorded, transcribed verbatim, and analysed using a phenomenological hermeneutical method. This narrative method enabled the researchers to reinterpret the worlds of the women with BC, as reflected in the data. The naïve understanding, ie, the meaning of the text as a whole, revealed that the participants were in a process of accepting and adapting to their life after ALND involving adjuvant chemotherapy and/or hormonal therapy. Thus, six main themes emerged in the thematic structural analysis illustrating the meaning of acceptance and adaptation when suffering from BC and undergoing a treatment trajectory, ie, establishing coherence, adjusting to treatment, safeguarding social belonging, re-defining oneself, feeling vulnerable, and accepting one's circumstances. If healthcare professionals provided structure and consistency, the women's treatment and lived experiences made sense; the women experienced more certainty, freedom, and meaningful social interactions. Uncertainty occurred when the women became lost in their own sense-making process, leading to low self-efficacy. There is a need for a paradigm shift in surgical care from viewing women with BC as anatomical constructions in need of repair to deeply understanding that they are persons with an illness who require ongoing self-management support.

Active symptom monitoring for premenopausal women with breast cancer initiating adjuvant endocrine therapy: Protocol for the SWOG S2010 randomized controlled efficacy trial

BackgroundPremenopausal women with early stage, high risk hormone receptor positive breast cancer are at risk of early discontinuation of adjuvant endocrine therapy (ET), primarily because of toxicity, which can increase the risk of disease recurrence and death. We hypothesize that identification of bothersome symptoms between clinic visits, and automated notification of clinicians about symptoms, will result in improved persistence with ET. MethodsPre- and perimenopausal women planning to receive adjuvant treatment with tamoxifen or an aromatase inhibitor plus ovarian function suppression or ablation for treatment of breast cancer are eligible. A total of 540 participants will be enrolled and randomized 1:1 to patient education with or without Active Symptom Monitoring (ASM). The ASM intervention includes 6 symptom questions (hot flashes, sadness, anxiety, insomnia, vaginal dryness, joint pain) that will be completed via text, email, or telephone weekly for 24 weeks, then every 4 weeks for 48 weeks. All participants will complete a battery of questionnaires every 12 weeks to examine symptoms, beliefs about medicine, self-efficacy, and ET adherence. Optional blood draws will be collected at baseline and after 12, 48, and 72 weeks of therapy to examine estradiol and ET concentrations. The primary endpoint is time to nonpersistence with initially prescribed ET within the first 72 weeks, evaluated using Kaplan-Meier plots and multivariable Cox regression. ConclusionWe expect early identification and management of ET-related toxicities to improve persistence with breast cancer therapy, breast cancer outcomes, and quality of life for premenopausal women at high risk of breast cancer recurrence.Clinicaltrials.govNCT05568472

Adjuvant endocrine therapy and risk of contralateral breast cancer: a systematic review and meta-analysis of observational studies.

Randomized clinical trials support reductions in contralateral breast cancer (CBC) risk with use of adjuvant endocrine therapy, however, real-world treatment effects, particularly for subgroups of breast cancer survivors, remain inconclusive. To address this, population-based observational studies of adjuvant endocrine therapy and CBC were synthesized and meta-analyzed. PubMed and Embase databases were systematically searched for observational studies of endocrine therapy use and CBC risk. Random effects meta-analyses estimated summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between endocrine therapy (ever use of tamoxifen and/or aromatase inhibitors (AIs)) and CBC risk. Heterogeneity across studies was assessed using the I2 test. Subgroup analyses were conducted by study design, menopausal status, and CBC estrogen receptor (ER)-status. Seventeen eligible observational studies (n = 287,576 breast cancer survivors) published between 1995 and 2019 were included. Endocrine therapy use was associated with reduced CBC risk (RR:0.62, 95% CI:0.53, 0.73, I2 = 84.8%, p < 0.0001). No heterogeneity was observed by study design (phet = 0.9). Similar reductions were observed in analyses restricted to tamoxifen use. As only two studies assessed AI use, estimates could not be meta-analyzed. In subgroup analyses, there were no differences in CBC risk reduction by menopausal status (phet = 0.22). Endocrine therapy reduced risk of ER-positive (RR:0.55, 95% CI:0.43, 0.70) but not ER-negative CBC (RR:1.26, 95% CI:0.95, 1.66) (phet < 0.001). This meta-analysis of observational studies supports a reduction in CBC risk with endocrine therapy among breast cancer survivors, in concert with evidence synthesized from randomized clinical trials, and highlights differences in endocrine therapy effectiveness by ER-status of CBC.

Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14–13/PrE0109)

BackgroundBidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC).MethodsPALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression’s value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models.ResultsFrom the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 – 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS.ConclusionsIn this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.

Electrochemotherapy to Treat a Single Thoracic Metastasis in Patient with Breast Cancer

Electrochemotherapy represents one of the therapeutic breakthroughs in the oncology field. In this case report, we describe a woman diagnosed with breast cancer in 2005. The case was treated surgically with right breast mastectomy, with axillary dissection for estrogen receptor positive ductal carcinoma, followed by a course of chemotherapy. Radiotherapy and hormonal adjuvant therapy with aromatase inhibitor were used for 8 years and the treatment plan was completed in 2014. After 17 years from the surgery, a thoracic Hight Resolution Computed Tomography scan showed a single node localized in right intercostal space, treated with a loco-regional treatment without complications. This allowed us to make the patient disease-free again. This case opens a choice in a loco-regional treatment to offer at a patient a new chance.

Updates in Systemic Treatment of Hormone Receptor-Positive Early-Stage Breast Cancer.

Hormone-receptor positive (HR +) and human epidermal growth factor receptor 2 (HER2) negative early breast cancer (eBC) is a heterogeneous disease with several contributing factors for increased risk of recurrence, including tumor features, individual biomarkers, and genomic risk. The current standard approach in the management of HR + /HER2neg eBC includes chemotherapy and endocrine therapy (ET), and additional therapies based on risk profile, menopausal status, and genetics are sometimes appropriate. The risk of recurrence is more pronounced in patients with high-risk eBC including large tumor size, nodal involvement, high proliferative index, and genetic predisposition. In premenopausal patients with high-risk eBC, ovarian function suppression in combination with adjuvant ET improves survival. In postmenopausal patients, extended aromatase inhibitor (AI) therapy can be considered. Recent trials have identified novel treatment approaches to reduce the risk of recurrence in high-risk HR + /HER2neg eBC including the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to adjuvant ET. For patients with germline BRCA1/BRCA2 mutations, adjuvant poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been shown to improve overall survival (OS). However, despite these recent advances, the risk of recurrence remains substantial, highlighting an area of unmet need. There are several ongoing clinical trials further investigating the role of CDK 4/6 inhibitors and immunotherapy in high-risk HR + /HER2neg eBC.

Coping With Side Effects: A Daily Diary Study in Women With Breast Cancer Living With Adjuvant Endocrine Therapy.

Adjuvant endocrine therapy (AET) is increasingly being prescribed for up to 10years to people diagnosed with hormone receptor-positive breast cancer. AET intake is often accompanied by side effects that significantly impact the well-being of people. The way individuals cope with medication-related side effects might play a pivotal role in their emotional adaption. This intensive-longitudinal study investigated the association between self-reported coping strategies (Brief COPE) and psychological well-being (Patient Health Questionnaire-4) among women undergoing AET. A multilevel factor analysis resulted in the identification of four coping factors, namely, problem-focused, support-focused, meaning-focused, and avoidance-focused coping. Daily coping efforts and experienced side effects were analyzed as predictors of psychological well-being using multilevel modeling. A total of 215 women (Mage=56.5±10.9years) participated, resulting in a total of n=2080 daily surveys (M=9.67±1.08). On average, women reported 3.7±2.2 different side effects per day. Days characterized by an elevated frequency of side effects and increased burden were associated with diminished well-being. Using more problem- and meaning-focused strategies than usual to cope with side effects correlated positively with well-being. Conversely, employing more support- and avoidance-focused coping strategies than usual was linked to reduced psychological well-being. Exploratory analyses focusing on individual coping strategies provided nuanced insights into coping behaviors. The present findings underscore the relationship between women's coping efforts concerning medication-related side effects during AET and their daily well-being. Psychosocial education (e.g., cognitive behavioral therapy) may offer valuable benefits for patients by helping them develop adaptive coping strategies to manage side effects.

Understanding health literacy's moderating role in remote monitoring for adjuvant endocrine therapy: Findings from a randomized clinical trial.

45 Background: Despite the efficacy of oral adjuvant endocrine therapy (AET) for improving survival among women with hormone receptor-positive early-stage breast cancer, adherence rates remain low. Our THRIVE study (NCT03592771) investigated the effectiveness of a mobile health remote monitoring app with and without tailored educational messages on AET adherence among women with breast cancer and found no statistically significant treatment effects on 1-year AET adherence overall. Health literacy contributes to patients’ understanding of their treatment plans. We conducted a post hoc analysis of the THRIVE study to examine if health literacy moderates the effectiveness of this intervention. Methods: This non-blinded randomized controlled trial included women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across three states. Participants used a pillbox to electronically monitor AET adherence for 1 year and completed surveys at enrollment. Consented participants were randomized into (1) “App”, receiving access to the study adherence and symptom monitoring app for 6 months, with increasing/severe symptoms and missed doses reported in the app triggering follow-ups from the oncology team; (2) “App+Feedback”, receiving additional weekly text messages about managing symptoms, adherence, and communication for 6 months; or (3) “Enhanced Usual Care (EUC).” The primary outcome was 1-year AET adherence captured with the pillbox (≥80% Proportion of Days Covered [PDC] vs. &lt; 80%). The enrollment survey captured participant’s sociodemographic characteristics, including race and ethnicity, education, household income, and health literacy. We used a linear probability model to measure the interaction between the study arm and health literacy on AET adherence. Results: Among 304 women randomized (104 EUC, 98 App, and 102 App+Feedback), the 12-month follow-up retention rate was 88% (n = 266) and 19.4% reported low health literacy at enrollment. Low health literacy was more prevalent among Black (29.4%) vs. White (13.4%) participants (p &lt; 0.001), those with incomes below the federal poverty level (34.4% vs. 17.2% of those with higher incomes, p = 0.02), and those with only a high school degree or lower education (31.7%) vs. with those with some college or higher education (16.4%, p &lt; 0.01). In the low health literacy group, 80.0% of App+Feedback were AET adherent vs. 42.1% of EUC, a 37.9 percentage point (ppt) difference (95% CI: 4.1 to 71.7, p = 0.03); in higher literacy group adherence, 47.1% of App+Feedback vs. 59.0% of EUC were adherent, a -11.8 ppt difference (95% CI: -27.9 to 4.3, p = 0.15). Conclusions: A remote monitoring app with tailored educational text messages led to higher 1-year AET adherence among participants with low health literacy, but not for those with high health literacy. Clinical trial information: NCT03592771 .

Unveiling the Clinical Path of Microinvasive Breast Cancer: A Comparative Study With Tis-T1 Breast Cancer.

The prognosis of microinvasive breast cancer (MIBC) is controversial, with a high reported rate of local recurrence (LR). This study aimed to evaluate the characteristics, treatments, and prognosis of patients with MIBC compared to those with carcinoma insitu (CIS) or early invasive cancer. Patients who diagnosed with CIS or stage I breast cancer were retrospectively enrolled. Using the Kaplan-Meier method, local recurrence-free survival (LRFS), systemic recurrence-free survival (SRFS), and cancer-specific survival (CSS) were compared according to T stage. The prognostic factors associated with LRFS were identified using the Cox proportional hazards model. According to T stage, 517 (21.6%), 200 (8.4%), 207 (8.7%), 363 (15.2%), and 1101 (46.1%) patients had Tis, T1mi, T1a, T1b, and T1c tumors, respectively. The proportion of human epidermal growth factor receptor 2-positive tumors was significantly higher in patients with MIBC (p < 0.0001). The administered adjuvant treatments also showed differences according to T stage (p < 0.0001). During the 73-month median follow-up period, patients with MIBC showed significantly worse LRFS than those with T1a or T1c tumors (p = 0.002). There was no significant difference in SRFS and CSS. In the Cox regression analysis, tumor multiplicity (p = 0.017), Ki-67 (p = 0.025), cancer subtype (p = 0.034), adjuvant endocrine therapy (p = 0.003), and adjuvant radiation therapy (p < 0.0001) were significant prognostic factors associated with LRFS. The risk of LR was higher in patients with MIBC than in those with small invasive breast cancer. Therefore, if indicated, adjuvant endocrine and radiation therapies should be administered to prevent undertreatment in patients with MIBC.

A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial

NATALEE assessed efficacy and tolerability of 3 years of adjuvant ribociclib plus NSAI compared with a nonsteroidal aromatase inhibitor (NSAI) alone in a broad population of patients with HR+/HER2- early breast cancer, including a select group without nodal involvement. This is the final preplanned analysis of invasive disease-free survival (iDFS). Premenopausal/postmenopausal women and men were randomized 1:1 to ribociclib (n=2549; 400 mg/day, 3 weeks on/1 week off for 36 months) plus NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 60 months) or NSAI alone (n=2552). Men and premenopausal women also received goserelin (3.6 mg once every 28 days). Patients had anatomical stage IIA (N0 with additional risk factors or N1), IIB, or III disease. The primary endpoint was iDFS. Secondary efficacy endpoints were recurrence-free survival (RFS), distant DFS (DDFS), and overall survival (OS). This final iDFS analysis was planned after ≈500 events. At data cutoff (21 July 2023), ribociclib was stopped for 1996 patients (78.3%); 1091 (42.8%) completed 3 years of ribociclib, and ribociclib treatment was ongoing for 528 (20.7%). Median follow-up for iDFS was 33.3 months. Overall, 226 and 283 iDFS events occurred with ribociclib plus NSAI vs NSAI alone, respectively. Ribociclib plus NSAI demonstrated significant iDFS benefit over NSAI alone (Hazard Ratio 0.749, 95% Confidence Interval [CI] 0.628-0.892; P=0.0012). The 3-year iDFS rates were 90.7% (95% CI 89.3%-91.8%) vs 87.6% (95% CI 86.1%-88.9%). A consistent benefit was observed across prespecified subgroups, including stage (II/III) and nodal status (+/-). DDFS and RFS favored ribociclib plus NSAI. OS data were immature. No new safety signals were observed. With longer follow-up and most patients off ribociclib, NATALEE continues to demonstrate iDFS benefit with ribociclib plus NSAI over NSAI alone in the overall population and across key subgroups. Observed adverse events remained stable.

Longitudinal Trends in Patient-Reported Outcomes in the First Year After Lumpectomy Versus Mastectomy.

It is unclear how patient-reported outcomes (PROs) change longitudinally after breast cancer surgery. We sought to compare trends in PROs among patients who underwent lumpectomy versus mastectomy over the first year after surgery. Newly diagnosed stage 0-III female patients with breast cancer who underwent lumpectomy or mastectomy at an academic breast center between June 2019 and March 2023 were invited to participate in a longitudinal PRO study. Enrolled patients received the BREAST-Q™ module, a validated tool measuring domains, such as satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. Scores for each domain were compared between the lumpectomy and mastectomy groups over the first year after surgery. Linear mixed models were used to estimate the change in PRO scores over time. The cohort included 203 who underwent lumpectomy and 144 who underwent mastectomy. Patients who underwent lumpectomy were older, more likely to receive adjuvant radiation and endocrine therapy, and less likely to receive adjuvant chemotherapy. Patients who underwent lumpectomy demonstrated greater increases in scores over time for satisfaction with breasts, psychosocial well-being, and sexual well-being compared with patients who underwent mastectomy, after adjusting for the abovementioned covariates and receipt of reconstruction. The lumpectomy group had a larger decline in physical well-being over time compared with the mastectomy group. Patients who underwent lumpectomy demonstrated greater satisfaction with their breasts, psychosocial well-being, and sexual well-being but worse physical well-being over the first year after surgery compared with patients who underwent mastectomy. These results may help inform early-stage breast cancer patients making decisions about their surgical care.

Результаты хирургического лечения проляпса в области заднего сегмента тазового дна у пациенток с раком молочной железы на фоне эндокринной терапии

The cause of pelvic organ ptosis in women is damage or weakening of the connective tissue and muscle structures of the pelvic floor, which normally serve as a supporting framework for pelvic organs and are estrogen-dependent. Most women with receptor-positive breast cancer are prescribed adjuvant endocrine therapy after surgery to suppress estrogen levels. The authors investigated the results of surgery of posterior pelvic floor segment prolapse in this category of patients (n = 50). The study was conducted in a comparative aspect with a group of patients who do not suffer from breast cancer (n = 50). For anatomical correction of prolapse, posterior colporaphy, anterior levatoroplasty or sphincterolevatoroplasty, resection of rectal mucosa prolapse using the STARR method, sacrocolporectopexy, depending on the pathology of certain structures of the pelvic floor, were performed. The evaluation of the treatment results was carried out after 3 years using clinical, radiological (defecography) and physiological methods (anorectal functional tests) studies. The authors showed that the symptoms of obstructive defecation and anal incontinence were less amenable to correction in patients with endocrine therapy. The authors concluded that it is necessary to prevent pelvic organ prolapse and the advantages of surgical correction of the initial forms of prolapse in this group of patients.