Henry Gomez

Trastuzumab is a cornerstone of treatment for HER2-positive breast cancer. Infusion-related reactions are common during the first administration, but severe reactions with hemodynamic instability and acute respiratory compromise are uncommon. We report a 36-year-old woman with de novo HER2-positive metastatic breast cancer involving the lungs who developed hypotension, presyncope, oxygen desaturation, and acute hypoxemic respiratory failure 35 minutes after the initiation of her first trastuzumab infusion. Chest computed tomography showed known bilateral pulmonary metastases and new bibasal opacities, raising concern for an overlapping severe infusion-related reaction and inflammatory pulmonary toxicity. Trastuzumab was discontinued, and the patient recovered after respiratory support and systemic corticosteroids. Following complete clinical recovery and resolution of the inflammatory radiological findings, a multidisciplinary team performed a rapid drug desensitization protocol under intensive care monitoring. The full trastuzumab target dose was successfully administered without immediate or delayed breakthrough reaction, and the protocol was repeated in subsequent 12 total cycles, allowing continued HER2-targeted therapy without disease progression. This case illustrates that rapid drug desensitization may permit trastuzumab reintroduction after a severe immediate infusion-related reaction in carefully selected patients once suspected pulmonary toxicity has fully resolved. Desensitization should not be interpreted as protection against recurrent drug-induced pneumonitis and requires individualized risk–benefit assessment, allergy evaluation, pulmonary reassessment, and administration in a specialized setting.

Purpose: Breast cancer (BC) is the most common malignancy in women and a leading cause of cancer-related mortality in Latin America (LATAM). This region is characterized by marked disparities in incidence, mortality, and care delivery, yet these differences have not been systematically examined. Methods: The LATINA study is a multinational, prospective cohort design to characterize BC in LATAM, enrolling patients 18 years and older with newly diagnosed BC across 10 countries. Data collection occurred at baseline and every 6 months for up to 5 years postenrollment. Multivariable logistic regression was used to identify associations between advanced-stage diagnosis and the detection method. Causal mediation analysis evaluated whether the detection method mediated the association between the type of health care coverage (public v private) and the stage at diagnosis. Results: Among 3,275 patients, 72.1% received care in public health systems and 41.8% were 50 years and younger. Overall, 40.5% presented at an advanced stage (III or IV). The most common molecular subtypes were luminal A (41.3%) and human epidermal growth factor receptor 2 (HER2)–positive (22.9%). Most patients were diagnosed based on symptoms (60.3%). Symptom-detected disease was more frequent among patients in the public health system (68.3% v 59.6% private; P < .001). In multivariable analyses, younger age (≤40 years), public health care coverage, symptom-detected disease, and HER2 overexpression were independently associated with advanced-stage presentation. Younger age, Black or African American/Brown race, public health care coverage, lower educational attainment, unemployment, unmarried status, and triple-negative disease were associated with symptom-detected diagnosis. Conclusion: A substantial proportion of BC cases in LATAM are diagnosed symptomatically and at advanced stages. Late-stage presentation is associated with sociodemographic characteristics and type of health care coverage. Strategies that expand screening programs and strengthen early diagnosis will be essential to improve early detection and reduce disparities in BC outcomes across LATAM.

Figure S1, Figure S2, Figure S3, Table 1 References.

Purpose: The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway is frequently activated in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, with loss of phosphatase and tensin homolog (PTEN) activity contributing to this activation. Capivasertib is a potent pan-AKT inhibitor, approved in combination with fulvestrant for the treatment of HR-positive/HER2-negative locally advanced/metastatic breast cancer with one or more PIK3CA/AKT1/PTEN tumor alterations. Next-generation sequencing (NGS) is commonly used to identify patients with PIK3CA/AKT1/PTEN tumor alterations. However, the utility of immunohistochemistry (IHC) to identify patients with PTEN-deficient tumors has not been explored in this context. Experimental Design: This exploratory analysis was based on tumor samples collected from patients in the global phase III CAPItello-291 study. Results: PTEN IHC results were obtained for 367 tumor samples, with 70 (19.1%) identified as PTEN deficient by IHC. A total of 346 (94.3%) samples with a PTEN IHC test result also had NGS test results available for PIK3CA/AKT1/PTEN alteration status. When comparing PTEN deficiency by IHC with PTEN alteration status by NGS, the overall, positive, and negative percent agreements were 87.0% (301/346), 71.9% (23/32), and 88.5% (278/314), respectively. Exploratory analysis in patients with PTEN-deficient tumors by IHC (n = 70) showed improved progression-free survival in the capivasertib plus fulvestrant versus placebo plus fulvestrant treatment arm (median 9.3 vs. 3.7 months; hazard ratio: 0.52, 95% confidence interval, 0.28–0.90). Conclusions: These results suggest potential utility for IHC in determining tumor PTEN status in breast cancer and raise the possibility of IHC identifying additional patients who could benefit from treatment with capivasertib and fulvestrant.

Supplementary Data from Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

Supplementary Figure S1 shows the expression of the 50 genes in the PAM50 signature, obtained from the 164-gene codeset.

Supplementary Figure S4 shows a forest plot of the exploratory categorical analysis of selected (meta)gene expression and their association with disease free survival on the capecitabine arm vs. observation.

Supplementary Table S1 shows the gene list for the NanoString custom nCounter codeset included in the study. Supplementary Table S2 shows patient characteristics in the GEICAM/CIBOMA translational study cohort versus the original trial. Supplementary Table S3 shows the distribution of PAM50 intrinsic subtypes in the GEICAM/CIBOMA translational study cohort. Supplementary Table S4 shows the differential gene expression analysis performed on the 164 genes included in the custom codeset comparing PAM50 non-basal vs. basal-like subtype and their biological processes. Supplementary Table S5 shows multivariate survival analysis and interaction tests for the four genes and metagenes included in the prespecified hypotheses testing their association with DFS. Supplementary Table S6 shows multivariate survival analysis and interaction tests for the continuous expression of the 38 individual genes included in the prespecified hypotheses testing their association with DRFS. Supplementary Table S7 shows multivariate survival analysis and interaction tests for the continuous expression of the 38 individual genes included in the prespecified hypotheses testing their association with OS. Supplementary Table S8 shows multivariate survival analysis and interaction tests for the continuous expression of the 38 individual genes included in the prespecified hypotheses testing their association with DFS. Supplementary Table S9 shows multivariate survival analysis and interaction tests restricted to the PAM50 non-basal subgroup. Supplementary Table S10 shows Exploratory analysis for the prognostic capacity of the continuous expression of genes and metagenes restricted to the PAM50 non-basal subgroup.

Supplementary Data S1 shows exploratory analysis for the predictive capacity of the continuous expression of additional genes and metagenes included in the codeset. Supplementary Data S2 shows exploratory analysis for the prognostic capacity of the continuous expression of the selected genes and metagenes

Supplementary Figure S2 shows a forest plot comparing basal vs. non-basal subtype as defined by PAM50 or by IHC, and their associations with disease free survival on capecitabine vs. observation arm.