Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies

Abstract

The addition of targeted therapies (TT) to endocrine therapy (ET) has improved the outcomes of patients with HR-positive, HER2-negative metastatic breast cancer (mBC). However, it is unknown whether patients with invasive lobular carcinoma (ILC) or mixed invasive ductal and lobular carcinoma (mixed) histologies experience the same magnitude of benefit from this therapy as those with invasive ductal carcinoma (IDC). We aim to determine whether patients with IDC, ILC, and mixed HR+/HER2− mBC derive similar benefit from the addition of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is), mammalian target of rapamycin inhibitor (mTORi), and phosphoinositide 3-kinase inhibitor (PI3Ki) to ET in HR+/HER2− mBC. We conducted an observational, population-based investigation using data from the MD Anderson prospectively collected database. We conducted a histology-based analysis of progression-free survival (PFS) and overall survival (OS) durations in 3784 patients with HR+/HER2− mBC who were treated with TT plus ET between January 1, 2010, and December 31, 2021. Out of the 3784 patients, 2975 were included in the final analysis. Of these, 2249 received CDK4/6is (81% IDC, 15% ILC, and 4% mixed), 1027 received everolimus (82% IDC, 14% ILC, and 4% mixed) and 49 received alpelisib (81% IDC and 19% ILC). The addition of targeted therapy to ET did not result in statistically significant differences in PFS or OS duration among patients with IDC, ILC, and mixed HR+/HER2− mBC. We concluded that for patients with HR+/HER2− mBC, the addition of TT to ET leads to a similar magnitude of benefit, irrespective of histology.

Reporting on invasive lobular breast cancer in clinical trials: a systematic review

“…Unfortunately, histological subtyping was missing for more than half of the patients in these pooled analyses, and as a result, the analyses for ILC were performed only on a small number of patients ( n = 269). Several retrospective studies came to a similar conclusion that the benefit of CDK4/6 inhibitors is similar for metastatic ILC in comparison to IBC-NST 43 , 44 .…”

“…Limited data exist that there is no significant difference in the benefit of everolimus between patients with metastatic ILC vs. IBC-NST 43 . A retrospective study concluded that patients with ILC benefit more from the combination of exemestane with everolimus than the combination of palbociclib with fulvestrant when used in second line of metastatic treatment in patients with hormone-resistant disease 45 .…”

Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors

“…However, several of these studies were limited by a low number of patients included 7 , 8 , or by the fact that the prognostic role of HER2 status was evaluated in heterogeneous patient cohorts, i.e., in patients with different tumor biology and receiving different types of systemic therapies 6 , 9 . A recent, large study from the MD Anderson Cancer Center did not find an association between HER2 status and clinical outcomes in 919 HR + /HER2- aBC patients treated with first-line ET plus CDK4/6 inhibitors 15 . Discrepancies across studies could derive from differences in the population of patients included (e.g., different patient- and tumor-related characteristics), diverse assessment of HER2 status, different clinical management of patients (e.g., different types of backbone ET or CDK4/6i compound used, different subsequent lines of therapy, and in particular T-DXd), or the inclusion of patients with different intrinsic BC subtypes 16 .…”

Novel rod‐like carbon nanomaterials as near infrared‐responsive drug delivery system for potential anticancer applications

“…Due to their serious metastasis and secondary infection, cancers have been the leading cause of human death. The general treatments of cancer include surgery [1,2], chemotherapy [3,4], radiotherapy [5,6], and so on. With the rapid development of nanotechnology and materials science [7][8][9][10], nano-drug delivery systems [11][12][13][14] have been widely concerned in the cancers' diagnosis [15] and treatment [16].…”