Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6–15

BACKGROUND:The effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18. PATIENTS AND METHODS:Participants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR). RESULTS:A total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P = 0.98). No new safety signals were identified. CONCLUSIONS:The efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.

In NeoTRIP (NCT002620280) addition of atezolizumab to nab-paclitaxel/carboplatin was linked to minor numerical increase of pathologic complete response (pCR) in women with high-risk TNBC (48.6 vs 44.4%, p = 0.48), which was 7.6% higher in PD-L1 positive tumors treated with atezolizumab (Gianni L et al, Annal Oncol 2022).

Estimating the risk of late distant recurrence (DR) is an important goal for the management of hormone receptor-positive (HR+) early breast cancer (EBC) patients (pts) after 5 years of endocrine treatment (ET) without recurrence. The Clinical Treatment Score post–5 years (CTS5) tool was developed to estimate residual risk of Distant Recurrence (DR) after 5 years of ET (Dowsett 2018). CTS5 is a continuous score based on 4 clinical variables (number of positive nodes, tumor size, grade, and age) which distributes HR+/human epidermal growth factor receptor-negative (HER2-) EBC pts in 3 risk of DR groups depending on the score (low-risk: <3.13, intermediate-risk: 3.13-3.86 and high-risk: > 3.86). We performed a retrospective analysis of 5739 HR+/HER2- EBC pts to validate the CTS5 score as prognostic tool of late relapse, beyond 5 years. They were selected from El Álamo IV registry with pts diagnosed between 2002 and 2005 (N=3061) and 4 adjuvant GEICAM studies (9805, 9906, 2003-02 and 2003-10; N=2678) carried out from 1996 and 2006. Pts had to be distant recurrence free at 5 years from ET initiation. CTS5 classified 43.9% as low-risk, 32.2% as intermediate-risk and 23.9% as high-risk. A significant difference in DR was seen among the three groups, HR intermediate-risk vs low, 2.55 (95% CI, 1.85 to 3.52) and HR high-risk vs low, 5.77 (95% CI, 4.28 to 7.78). The continuous CTS5 (range: 1.2 - 6.06) was significantly prognostic (HR, 2.31; 95% CI, 2.05 to 2.61). DR percentage expected and observed by subgroups are described in the table. The CTS5 was able to classify Spanish patients according to different risk of late DR, independently of menopausal status, ET duration or CT treatment. However, the model seems to overestimate the number of events particularly in the high-risk group. This overestimation was more pronounced among patients treated with ET for less than 60 months or those not receiving CT.

Breast cancer (BC) mostly occurs in women over 50 years old, however, around 5% of cases are very young women (BCVY) (age ≤35) being associated to poorer prognosis and shorter survival. Age-associated differences in BC remain poorly studied. Understanding biological differences in BCVY may lead to better therapeutic options for these patients. This work aimed to identify molecular differences between breast tumors from BCVY and old women (BCO). The formalin-fixed samples of a retrospective cohort (N = 49) collecting treatment naïve core needle biopsies from 22 BCVY and 27 BCO (age ≥ 50) were analyzed. A preanalytic sample selection was performed to assess the quality before the RNA sequencing (HiSeq X Series, Illumina). Wilcoxon test was used on normalized RNA-seq data to compare the BCVY and BCO groups. All analyses were performed using R software (v 4.0.2). The BCVY cohort included 12 (55%) luminal, and 10 (45%) non-luminal BCs, while the BCO cohort was 17 (63%) luminal and 10 (37%) non-luminal patients. Principal Components Analysis of mRNA-seq data revealed a higher heterogeneity among BCVY. Age-related gene expression differences were confirmed (40 and 13 genes down- and up-regulated [fold change ± 2]). BCVY presented higher chromosomal instability (CIN70, p= 1e-06) and were more immunoreactive tumors presenting significantly higher scores in immune-related gene signatures (inflammation, cytokines, IFN gamma, macrophages, Th2 cells, B cells, DC, and IGG). Moreover, BCVY tumors were more proliferative as confirmed by higher expression of related gene signatures (p= 5.17e-05) and ki67 (IHC, p= 0.021). These findings were particularly significant in luminal BC. Interestingly, despite there were no differences in ER and PR by IHC, lower expression was found at RNA level in luminal BCVY patients (ESR1: p= 0.0027, PGR: p= 0.0476). Our study provides novel findings on the impact of aging on transcriptional landscape in BC. We found age-related gene expression changes not only in cancer cells but also in the tumor microenvironment. These data suggest that luminal BCVY could be more endocrine-resistant and aggressive than BCO. Therefore, this work highlights age as an important factor to be considered in clinical practice.

Adjuvant anthracyclines and taxanes reduce risk of recurrence and death in Early Breast Cancer (EBC) patients (pts) but the toxicity profile is a major concern. Several studies have shown conflicting results correlating Body Mass Index (BMI) and outcomes in these pts. There are limited data on the efficacy of adjuvant taxanes among BMI categories. The prognostic effect of BMI on disease recurrence between adjuvant Paclitaxel (P)-based Chemotherapy (CT) vs. Docetaxel (D)-based CT has not ever been reported. Pt-level pooled analysis of 13,486 EBC pts treated with adjuvant anthracyclines +/- taxanes from 7 GEICAM & TRIO adjuvant randomized controlled trials (RCTs) carried out from 1996 to 2008. Pts were classified in 4 BMI (kg/m2) categories: normal (< 25.0), overweight (25.0 to 29.9), obese (30.0 to 34.9), and severely obese (≥ 35.0), to evaluate BMI as a predictive factor for efficacy and toxicity of adjuvant taxane-based CT. Hazard Ratios (HR) were calculated using a Cox proportional hazard model stratifying by RCT. Pts distribution based on BMI was: 44% normal, 33% overweight, 16% obese, and 8% severely obese. 79% were treated with taxane-based CT (83% with D and 17% with P). 10y iDFS was 71%, 70%, 68% and 64% in normal, overweight, obese, and severely obese pts who received CT, respectively, being statistically significant in obese (HR 1.15; 95% CI 1.05-1.26; p=0.002) and severely obese (HR 1.29; 95% CI 1.15-1.45; p<0.001). 10y iDFS by type of CT are describe in the table. Relevant toxicity was 5%, 5.5%, 5.9% and 9.3% in normal, overweight, obese, and severely obese pts who received D.Table: 251PNormalOverweightObeseSeverely obeseD vs. non- D70% vs. 62% HR 0.7395% CI 0.59-0.89 p=0.00367% vs. 66%HR 0.8395% CI 0.66-1.05 p=0.12466% vs. 62%HR 0.8495% CI 0.61-1.16 p=0.28564% vs. 67%HR 1.1295% CI 0.70-1.78 p=0.646P vs.non-P79% vs. 77%HR 0.9495% CI 0.75-1.17 p=0.55477% vs. 74HR 0.8995% CI 0.71-1.13 p=0.34778% vs. 72%HR 0.7295% CI 0.52-0.98 p=0.03971% vs. 65%HR 0.7095% CI 0.45-1.09 p=0.113 Open table in a new tab . Prognosis is worse in heavier vs. leaner EBC pts receiving adjuvant taxane-based CT. Leaner pts receiving D (compared to non-D) achieved a better outcome, while pts who benefited most from P were the obese subgroup (compared to non-P).

Sexual dysfunction is the most common long-term consequence of cancer treatment in breast cancer survivors (BCS), which have a huge impact on their quality of life (QOL). We pretend to develop a tool to assess these problems, identify the most relevant challenges, and prove the beneficial effect a nursing intervention would have on their QOL. This is a prospective study with 51 BCS treated with HT, who were recruited from Hospital Clínico Valencia, from March to April 2023. A questionnaire with 28 related items was developed, including demographical data. These were evaluated by a Likert scale. Patients were aged under 45 years-old (mean 40.5 + 3.2). 82.4% of BCS received previous chemotherapy treatment. Regarding the surgery, only 43.1% presented a tumorectomy. 21.6% of BCS were treated with Tamoxifen and 78.4% with aromatase inhibitors plus LH-RH analogues (AI + LHRHA). 70.6% expressed high satisfaction with their previous sexual life; however, only 25.5% of BCS feel satisfied. This study highlights vaginal dryness (72.5%), loss of sensibility in the affected breast (62.5%), loss of femininity (60.8%), loss of desire (60.8%), and fear of penetration pain (60.8%). AI + LHRHA was related to fear of penetration pain (p=0.003). The type of surgery impacted sexual satisfaction (p=0.031), and breast sensitivity (p=0.018). 74.5% of the patients emphasized the importance of sexual health. Nevertheless, 72.6% of BCS stated a decrease in the frequency of their sexual activity. 66.7% of the patients shared these issues with their partners, but only 23.6% talked about it with the oncologist. Furthermore, 72.5% felt that they did not have enough previous information. Interestingly, 80.4% would attend a nursing sexual health counselling and 78.4% considered this would improve their QOL. HT impacted BCS’ sexual health. The most frequent problems were dysfunction due to vaginal dryness, penetration pain, and desire. Mastectomy and AI + LHRHA presented poorer outcomes. Nurses’ interventions could be helpful to improve their QOL.

Introduction The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly regarding early cancer diagnosis, sparking public health concerns that possible delays could increase the proportion of patients diagnosed at advanced stages. In 2009, a cancer fast-track program (CFP) was implemented at the Clinico-Malvarrosa Health Department in Valencia, Spain with the aim of shortening waiting times between suspected cancer symptoms, diagnosis and therapy initiation. Objectives The study aimed to explore the effects of the COVID-19 pandemic on our cancer diagnosis fast-track program. Methods The program workflow (patients included and time periods) was analysed from the beginning of the state of alarm on March 16th, 2020 until March 15th, 2021. Data was compared with data from the same period of time from the year before (2019). Results During the pandemic year, 975 suspected cancer cases were submitted to the CFP. The number of submissions only decreased during times of highest COVID-19 incidence and stricter lockdown, and overall, referrals were slightly higher than in the previous 2 years. Cancer diagnosis was confirmed in 197 (24.1%) cases, among which 33% were urological, 23% breast, 16% gastrointestinal and 9% lung cancer. The median time from referral to specialist appointment was 13 days and diagnosis was reached at a median of 18 days. In confirmed cancer cases, treatment was started at around 30 days from time of diagnosis. In total, 61% of cancer disease was detected at early stage, 20% at locally advanced stage, and 19% at advanced stage, displaying time frames and case proportions similar to pre-pandemic years. Conclusions Our program has been able to maintain normal flow and efficacy despite the challenges of the current pandemic, and has proven a reliable tool to help primary care physicians referring suspected cancer patients.

Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.

Ipatasertib is a potent and selective small-molecule inhibitor of all three isoforms of the serine/threonine kinase AKT. Its beneficial use as a single-agent or in combination with chemotherapeutic, hormonal, or targeted agents for patients (pts) with metastatic breast cancer is supported by in vivo results. Pathfinder is evaluating the safety, tolerability, and preliminary efficacy of ipatasertib in combination with non-taxane chemotherapy agents in taxane-pretreated unresectable advanced TNBC.

PEARL study did not show superiority in progression-free survival (PFS) with P+ET versus (vs) CAP in patients (pts) with AI-resistant MBC, but P+ET was better tolerated and showed a significant delay in quality of life deterioration. Final OS data are reported here.

Background: Recently, microRNAs have been demonstrated to be potential non-invasive biomarkers for diagnosis, prognosis assessment or prediction of response to treatment in cancer. In this study, we evaluate the potential of miR-30b-5p as a biomarker for early diagnosis of breast cancer (BC) in tissue and plasma. Methods: Expression of miR-30b-5p was determined in a series of 112 BC and 40 normal breast tissues. Circulating miR-30b-5p levels in plasma samples were determined in a discovery cohort of 38 BC patients and 40 healthy donors and in a validation cohort of 83 BC patients and 83 healthy volunteers. miR-30b-5p expression was measured by quantitative real-time PCR and receiver operating characteristics curve analysis was carried out. Results: The miR-30b-Sp expression was significantly lower in BC tissue than in healthy breast samples. In contrast, circulating miR-30b-5p levels were significantly higher in BC patients compared with healthy donors. Furthermore, circulating miR-30b-Sp levels were significantly higher in patients with positive axillary lymph node and de novo metastatic patients. Receiver operating characteristics curve analysis demonstrated a good diagnostic potential of miR-30b-Sp to detect BC even at an early stage of the disease. Conclusion: Thus, we highlight the potential of miR-30b-Sp as a non-invasive, fast, reproducible and cost-effective diagnostic biomarker of BC.