mHealth technology as a help tool during breast cancer treatment: A content focus group

Purpose: To assess the usability and preferences of the contents of mHealth software developed for breast cancer patients as a tool to obtain patient-reported outcomes (PROMs), improve the patient’s knowledge about the disease and its side effects, increase adherence to treatment, and facilitate communication with the doctor. Intervention: an mHealth tool called the Xemio app provides side effect tracking, social calendars, and a personalized and trusted disease information platform to deliver evidence-based advice and education for breast cancer patients. Method: A qualitative research study using semi-structured focus groups was conducted and evaluated. This involved a group interview and a cognitive walking test using Android devices, with the participation of breast cancer survivors. Results: The ability to track side effects and the availability of reliable content were the main benefits of using the application. The ease of use and the method of interaction were the primary concerns; however, all participants agreed that the application would be beneficial to users. Finally, participants expressed their expectations of being informed by their healthcare providers about the launch of the Xemio app. Conclusion: Participants perceived the need for reliable health information and its benefits through an mHealth app. Therefore, applications for breast cancer patients must be designed with accessibility as a key consideration.Postprint (published version

Intrinsic Subtypes and Therapeutic Decision-Making in Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer with Visceral Crisis: A Case Report

Background: CDK4/6 inhibitors (CDKi), namely, palbociclib, ribociclib, and abemaciclib, combined with either an aromatase inhibitor (AI) or fulvestrant are the standard first/second line for hormone receptor-positive(HR+)/HER2-negative(neg) metastatic breast cancer (MBC). However, the choice of one specific CDKi is arbitrary and based on the physician's experience with the drug, toxicity profile, and patient's preferences, whereas biomarkers for optimal patient selection have not been established so far. Moreover, upfront chemotherapy is still recommended in case of clinical presentation with visceral crisis, despite no evidence of superior benefit for chemotherapy regimens against CDKi-based regimens. Recent correlative biomarker analyses from pivotal trials of palbociclib and ribociclib showed that HR+/HER2-neg MBC might respond differently according to the molecular intrinsic subtype, with Luminal A and B tumors being sensitive to both CDKi, Basal-like being insensitive to endocrine therapy, irrespective of CDKi, and HER2-enriched tumors showing a benefit only with ribociclib-based therapy. Clinical case: We hereby present a paradigmatic clinical case of a woman affected by a relapsed HR+/HER2-neg MBC with bone and nodal lesions, presenting with a visceral crisis in the form of lymphangitis carcinomatosis and diagnosed with a molecularly HER2-enriched tumor, successfully treated with upfront ribociclib + fulvestrant. The patient experienced a complete symptomatic and radiologic remission of the lymphangitis with a partial response as best response, according to RECIST 1.1 criteria. The progression-free survival (PFS) was of 20 months, in line with the median PFS observed in the ribociclib + fulvestrant pivotal trial, where, however, patients with visceral crisis had been excluded. Conclusions: This clinical case confirms in the real-world setting that non-luminal subtypes can be found in HR+/HER2-neg disease and may have potential therapeutic implications in the metastatic setting. It also questions the recommendation of upfront chemotherapy in the case of a visceral crisis in the era of CDKi-based regimens. These issues merit further evaluation in prospective and larger studies

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy.Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model.201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms.We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted

Significant Clinical Activity of Olaparib in a Somatic BRCA1-Mutated Triple-Negative Breast Cancer With Brain Metastasis

Breast cancer is a biologically and clinically heterogeneous disease, and patients with similar clinical stage have markedly different outcomes. Triple-negative breast cancer (TNBC) is defined by the lack of expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2).1,2 This subtype represents 15% to 20% of all breast cancers and is associated with the worst outcome of all subtypes, with greater tendency to distant recurrence in general and visceral metastasis in particular, including brain metastasis.3,4 To date, chemotherapy remains the standard of care for TNB

Frequency and spectrum of PIK3CA somatic mutations in breast cancer

Purpose: The therascreen PIK3CA mutation assay and the alpha-specific PI3K inhibitor alpelisib are FDA-approved for identifying and treating patients with advanced PIK3CA-mutated (PIK3CAmut) breast cancer (BC). However, it is currently unknown to what extend this assay detects most PIK3CA mutations in BC. This information is critical as patients and clinicians are using this and other genomic assays to indicate alpelisib. Methods: Data from 6338 patients with BC was explored across 10 publicly available studies. The primary objective was to evaluate the proportion and distribution of PIK3CA mutations in BC. Secondary objectives were (1) to evaluate in silico the spectrum of PIK3CA mutations in BC that would be captured by the therascreen panel; (2) to evaluate the proportion and distribution of PIK3CA mutations in hormone receptor-positive/HER2-negative (HR+/HER2-), HER2+, and triple-negative BC (TNBC); and (3) to explore the identification of PIK3CA mutations in a cohort of 48 HR+/HER2- advanced BC patients by the Guardant B360 circulating tumor DNA (ctDNA) assay. Results: Patients with PIK3CAmut tumors represented 35.7% (2261/6338). Five PIK3CA mutations comprised 73% of all PIK3CA mutations: H1047R (35%), E545K (17%), E542K (11%), N345K (6%), and H1047L (4%). Therascreen gene list would capture 72% of all PIK3CA mutations and 80% of patients with a known PIK3CAmut BC. Among patients with double PIK3CAmut tumors (12% of all PIK3CAmut), the therascreen panel would capture 78% as harboring 1 single PIK3CA mutation, 17% as PIK3CAmut undetected, and 5% as PIK3CA double-mut. PIK3CA mutation rates were lower in TNBC (16%) compared to HR+/HER2 (42%) and HER2+ (31%) BC; however, the distribution of the 4 main PIK3CA mutations across subtypes was similar. Finally, 28% of PIK3CA mutations identified in ctDNA in 48 patients with advanced HR+/HER2- BC were not part of the therascreen panel. Conclusion: PIK3CA mutations in BC are heterogenous and ~ 20% of patients with a known PIK3CA mutation, and 95% with a known double PIK3CAmut tumor, would not be captured by the therascreen panel. Finally, the clinical utility of PIK3CA mutations not present in the therascreen companion diagnostic assay or identified by other sequencing-based assays needs further investigation

Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial

Antecedents: L'assaig Opti-HER HEART tenia com a objectiu optimitzar l'activitat i minimitzar el risc cardíac combinant trastuzumab, pertuzumab i paclitaxel amb doxorubicina liposomal no pegilada en el tractament del càncer de mama precoç HER2-positiu. Mètodes: Els pacients amb càncer de mama HER2 positiu en fase II-IIIB van rebre trastuzumab neoadjuvant, pertuzumab, paclitaxel i una doxorubicina liposomal no pegilada cada tres setmanes durant sis cicles. El principal criteri final va ser la seguretat cardíaca durant la teràpia neoadjuvant. Es van avaluar els esdeveniments cardíacs tipus A (insuficiència cardíaca congestiva simptomàtica) i B (reducció asimptomàtica de la fracció d'ejecció del ventricle esquerre). Els criteris finals secundaris van incloure l'avaluació de la taxa de resposta patològica completa (pCR) i la taxa de resposta global, entre d'altres. Com a anàlisi exploratòria ad-hoc , es va mesurar l'expressió de 55 gens relacionats amb el càncer de mama, inclosos els gens PAM50 , en 58 mostres de tumors basals i 60 mostres quirúrgiques. Resultats: Es van reclutar vuitanta-tres pacients. La incidència d'esdeveniments cardíacs durant el tractament neoadjuvant va ser del 2,4%. No es va observar cap esdeveniment cardíac de tipus A. La taxa global de pCR va ser del 56,6% (interval de confiança (IC) del 95%: 45,3-67,5%). El subtipus enriquit amb HER2, que representava el 52,0% de totes les mostres basals, es va associar amb una taxa de pCR més alta en comparació amb els tumors no enriquits amb HER2 (83,3% vs. 46,3%; odds ratio 5,76; 95% CI 1,71-19,42). L'associació de subtipus amb pCR va ser independent de les variables clínicopatològiques conegudes, inclòs l'estat del receptor hormonal. En comparació amb les mostres basals, els exemplars quirúrgics van mostrar una significativa regulació descendent dels nivells relacionats amb la proliferació ( MKI67 i CCNB1 ) i ERBB2 , i una regulació ascendent significativa dels relacionats amb la llum (ESR1 i PGR ) i gens immunes ( CD8A ). Conclusions: La combinació de doble bloqueig HER2 amb trastuzumab i pertuzumab amb paclitaxel i doxorubicina liposomal no pegilada s'associa amb una baixa taxa d'esdeveniments cardíacs. El subtipus enriquit amb HER2 s'associa a una alta taxa de pCR

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Purpose: Prognostic and predictive biomarkers to cyclindependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA ( ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy. Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model. Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/ overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms. Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted

Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer

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

Serum Phospholipids Fatty Acids and Breast Cancer Risk by Pathological Subtype

This study evaluates whether serum phospholipids fatty acids (PL-FAs) and markers of their endogenous metabolism are associated with breast cancer (BC) subtypes. EpiGEICAM is a Spanish multicenter matched case-control study. A lifestyle and food frequency questionnaire was completed by 1017 BC cases and healthy women pairs. Serum PL-FA percentages were measured by gas chromatography-mass spectrometry. Conditional and multinomial logistic regression models were used to quantify the association of PL-FA tertiles with BC risk, overall and by pathological subtype (luminal, HER2+ and triple negative). Stratified analyses by body mass index and menopausal status were also performed. Serum PL-FAs were measured in 795 (78%) pairs. Women with high serum levels of stearic acid (odds ratio (OR)T3vsT1 = 0.44; 95% confidence interval (CI) = 0.30-0.66), linoleic acid (ORT3vsT1 = 0.66; 95% CI = 0.49-0.90) and arachidonic to dihomo-γ-linolenic acid ratio (OR T3vsT1 = 0.64; 95% CI = 0.48-0.84) presented lower BC risk. Participants with high concentrations of palmitoleic acid (ORT3vsT1 = 1.65; 95% CI = 1.20-2.26), trans-ruminant palmitelaidic acid (ORT3vsT1 = 1.51; 95% CI = 1.12-2.02), trans-industrial elaidic acid (ORT3vsT1 = 1.52; 95% CI = 1.14-2.03), and high oleic to stearic acid ratio (ORT3vsT1 = 2.04; 95% CI = 1.45-2.87) showed higher risk. These associations were similar in all BC pathological subtypes. Our results emphasize the importance of analyzing fatty acids individually, as well as the desaturase activity indices