Taxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously ...treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies.
We analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3–24 months after previous (neo)adjuvant taxanes treatment.
Of 23,501 female patients with MBC in ESME, 1057 met the selection criteria. 58.4% received a taxane-based regimen (75.4% concomitant bevacizumab) and 41.6% received other CT.
In hormone-receptor positive (HR+)/HER2- MBC, multivariate analysis showed no difference in OS between taxanes without bevacizumab compared to other CT (HZR = 1.3 0.97; 1.74, but taxanes was significantly associated with worse PFS (HZR = 1.48 1.14; 1.93).
In TNBC, taxanes without bevacizumab and carboplatin/gemcitabine were not superior to other CT for OS (HZR = 1.07 0.79; 1.44 and HZR = 0.81 0.58; 1.13, respectively), while for PFS, taxanes was inferior (HZR = 1.33 1.06–1.67) and carboplatin plus gemcitabine was superior to other CT (HZR = 0.63 0.46; 0.87).
For both subtypes, the worse outcome observed with paclitaxel was no longer observed with the addition of bevacizumab.
With the limitation of retrospective design, taxanes rechallenge in early metastatic relapse of BC may result in a worse PFS in TNBC and HR+/HER2- MBC, which was not observed with the addition of bevacizumab.
•Patients with HER2-advanced breast cancer (ABC) have often previously received taxanes in the (neo)adjuvant setting.•Current guidelines suggest a rechallenge by taxanes in ABC with DFI≥12 months, few data are available for DFI ≤24 months.•Taxane rechallenge in early metastatic relapse of BC (DFI ≤24 months) may result in a worse PFS in TNBC and HR+/HER2- ABC.•In TNBC, the addition of bevacizumab to taxanes improves PFS and OS for DFI ≤24 months.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The identification of BRCA1 and BRCA2 led to the introduction of genetic testing and counselling as part of routine breast and ovarian cancer care, with two objectives: individual treatment ...indications and personalised prevention of the risk of subsequent cancers; and family counselling provided to healthy relatives. Primary prevention options, including prophylactic surgery by nipple-sparing mastectomy and bilateral adnexectomy, have shown a level I evidence effects on cancer risk reduction and level IIA evidence on cancer-specific mortality. ...BRCA1/2 germline mutations are classified as IA evidence biomarkers in the European Society for Medical Oncology Clinical Action Scale for Molecular Targets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report the case of a patient with metastatic breast cancer who presented with an orthostatic headache. After a comprehensive diagnostic workup including MRI and lumbar puncture, we maintained the ...diagnosis of intracranial hypotension (IH). The patient was therefore treated with two consecutive non targeted epidural blood patches, resulting in the remission of IH symptoms for 6 months. IH in cancer patients is a rarer cause of headache than carcinomatous meningitis. As the diagnosis can be made by standard examination and the treatment is relatively simple and effective, IH deserves to be better known by oncologists.
Definition of therapy‐related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy‐related acute ...myeloid leukemia and therapy‐related myelodysplastic syndromes has been proposed. We aimed to describe the molecular landscape of TRMN at diagnosis, among 77 patients with previous gynecologic and breast cancer with a dedicated next‐generation sequencing panel covering 74 genes. We investigated the impact of clonal hematopoiesis of indeterminate potential‐associated mutations (CHIP‐AMs defined as presence at TRMN stage of mutations described in CHIP with a frequency >1%) on overall survival (OS) and the clinical relevance of a modified genetic ontogeny‐based classifier that categorized patients in 3 subgroups. The most frequently mutated genes were TP53 (31%), DNMT3A (19%), IDH1/2 (13%), NRAS (13%), TET2 (12%), NPM1 (10%), PPM1D (9%), and PTPN11 (9%). CHIP‐AMs were detected in 66% of TRMN patients, with no impact on OS. Yet, patients with CHIP‐AM were older and had a longer time interval between solid tumor diagnosis and TRMN. According to our modified ontogeny‐based classifier, we observed that the patients with TP53 or PPM1D mutations had more treatment lines and complex karyotypes, the “MDS‐like” patients were older with more gene mutations, while patients with “De novo/pan‐AML” mutations were younger with more balanced chromosomal translocations. Median OS within each subgroup was 7.5, 14.5, and 25.2 months, respectively, with statistically significant difference in multivariate analysis. These results support the integration of cytogenetic and molecular markers into the future TRMN classification to reflect the biological diversity of TRMN and its impact on outcomes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Opinion statement
Antibody drug-conjugates (ADCs) have revolutionized the treatment of many types of cancer, including breast cancer. Recently, two new ADCs have been approved, trastuzumab deruxtecan ...and sacituzumab govitecan; both have demonstrated impressive improvements in overall survival, trastuzumab deruxtecan in all three subtypes of metastatic breast cancer and sacituzumab govitecan in luminal and triple negative metastatic breast cancer. These drugs are the results of significant progress and innovation in the construction of the three components of an ADC, the monoclonal antibody, the payload, and the linker, and of the discovery of new target antigens. ADC engineering has profoundly changed the paradigm of cancer treatment, on one side being effective on tumors considered inherently resistant to the payload class of drugs and on the other side demonstrating activity in tumors with very low target expression. Yet, it is likely that we are just at the beginning of a new era as the identification of new targets and the introduction of new ADC constructs and combinations will expand the field of ADC rapidly over the coming years.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
•HER3 is overexpressed in all three breast cancer subtypes.•HER3 plays a central role in resistance to breast cancer treatments.•HER3 is a potent activator of PI3K/Akt signaling.•HER3 is particularly ...expressed in brain metastasis.•Many anti-HER3 therapies are under clinical development with promising outcomes.
Breast cancer is a heterogeneous disease, encompassing multiple different subtypes. Thanks to the increasing knowledge of the diverse biological features of each subtype, most patients receive personalized treatment based on known biomarkers. However, the role of some biomarkers in breast cancer evolution is still unknown, and their potential use as a therapeutic target is still underexplored. HER3 is a member of the human epidermal growth factors receptor family, overexpressed in 50%-70% of breast cancers. HER3 plays a key role in cancer progression, metastasis development, and drug resistance across all the breast cancer subtypes. Owing to its critical role in cancer progression, many HER3-targeting therapies have been developed over the past decade with conflicting findings. Next-generation antibody-drug conjugates have recently shown promising results in solid tumors expressing HER3, including breast cancer. In this review, we discuss the HER3 role in the pathogenesis of breast cancer and its relevance across all subtypes. We also explore the new anti-HER3 treatment strategies, calling into question the significance of HER3 detection as crucial information in breast cancer treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
1077 Background: In the clinical trial setting, T-DXd improves survival for patients with HER2+ and HER2-low metastatic breast cancer (MBC), and has also shown preliminary activity in HER2-0 MBC. ...Little real-world evidence is available on the performance of T-DXd. Methods: We conducted a retrospective observational study using the nationwide Flatiron Health electronic health record (EHR)-derived deidentified database to evaluate the real-world activity of T-DXd. We included patients with MBC who initiated T-DXd between 12/2019 and 1/2023. Tumors were categorized as HER2+ if positive at any timepoint, with HER2- cases further divided into HER2-low (IHC 1+ or 2+ not amplified) and HER2-0 (IHC 0) according to the last biopsy before T-DXd. Real world progression-free survival (rwPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 930 patients were included: 636 with HER2+, 268 with HER2-low and 26 with HER2-0 MBC. Among HER2- patients, 241 (82.0%) were HR+ and 53 (18.0%) were HR- (i.e., triple-negative). A total of 572 (61.5%) patients were White, 101 (10.9%) Black/African American, 88 (9.4%) Hispanic/Latino, 37 (4.0%) Asian and 132 (14.2%) other or missing. Median age was 59 range 25, 84 and patients received T-DXd in the following lines of therapy (LOT): 54 (5.8%) as 1 st line, 110 (11.8%) as 2 nd line, 179 (19.2%) as 3 rd line, 182 (19.6%) as 4th line and 405 (43.6%) as ≥5 th line. Median number of LOT for advanced disease prior to T-DXd were 3 and 4, respectively, for HER2+ and HER2- patients. In patients with HER2+ MBC, rwPFS and OS were 12.1 and 26 months after initiating T-DXd, respectively. The longest rwPFS, 14.9 months, was observed in the 1st or 2nd LOT, followed by 14.1 months in LOT 3, 12.4 months in LOT 4, and 10.8 months in LOT ≥5. In patients with HER2- MBC, median rwPFS and OS were 6.3 and 15.5 months, respectively. The longest median rwPFS of 8.1 months was observed in the 1st or 2nd LOTs, followed by 6.9 months in LOT 4, 6.2 months in LOTs ≥5, and 6.0 months in LOT 3. Outcomes with T-DXd by HER2 and HR status are provided (Table). Updated data with a larger sample size will be presented. Conclusions: In the largest dataset to date, T-DXd showed favorable real-world activity for treating MBC, although rwPFS appeared shorter than what observed in clinical trials. Encouraging rwPFS was observed in understudied groups, such as patients with triple-negative and HR+/HER2-0 MBC. Table: see text
To describe first-line treatment patterns, overall survival (OS) and real-world progression-free survival (rwPFS) in young women (<40) with metastatic breast cancer (mBC), as compared to women aged ...40-69.
Data on adult women diagnosed with mBC (2008-2017) were extracted from the ESME mBC database (NCT03275311) which includes consecutive patients starting first-line metastatic treatment in one of the 18 French Comprehensive cancer centers. We reported first-line therapeutic strategy and prognostic factors of OS and rwPFS for women aged < 40 and 40-69.
In total, 14,897 mBC women were included (1512 aged <40). HR+ /HER2- mBC was the most frequent subtype. First-line treatment differed between young patients and older ones for HR+ /HER2- and Triple Negative (TN) mBC. Median OS for women aged < 40 and 40-69, respectively, was 46.9 and 46.2 months for HR+ /HER2- mBC; 13.5 and 15.2 for TN mBC; and, 60.7 and 55.1 for HER2 + mBC. Median rwPFS under first line treatment was 11.6 and 11.9 months for HR+ /HER2- in women aged < 40 and 40-69, respectively; 5.5 and 5.9 for TN, and, 13.3 and 12.9 for HER2 + . Factors associated with shorter OS and rwPFS were similar for both women aged < 40 and 40-69 and included ≥ 3 metastatic sites, visceral metastases, and longer MFI, with time-varying effects observed for several prognostic factors.
Young women presented more frequently with TN and HER2 + subtypes and aggressive mBC than women aged 40-69 did. Prognostic factors of OS and rwPFS were quite similar between age groups and mBC subtypes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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