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(Triple Negative Breast Cancer)

Relevant Articles About Triple Negative Breast Cancer Research and Clinical Trials

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TNBC (Triple Negative Breast Cancer)CapecitabinePembrolizumabSacituzumab Govitecan-hziy (SG)ActiveUnited States 9NCT05633654Phase 3
Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician’s Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/NSABP B-63)

Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician’s Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/NSABP B-63)

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Ultrasound Cutoff for Nodal Burden in BC Management

KEY TAKEAWAYS

  • The study aimed to assess if axillary ultrasound can identify BC patients with limited nodal burden for upfront surgery.
  • The results showed that incorporating abnormal ultrasound-detected nodes into practice may guide upfront surgery versus gene assay testing or neoadjuvant chemotherapy.

Traditionally, chemotherapy is administered to non-stage IV breast cancer (BC) patients with metastatic nodes. However, findings from the RxPONDER trial indicate that chemotherapy may be unnecessary for certain patients with 1-3 metastatic nodes if their 21-gene assay recurrence score is ≤25.

Geok Hoon Lim and the team aimed to determine if axillary ultrasound can identify patients with minimal nodal involvement, allowing for surgery followed by gene assay testing to potentially avoid chemotherapy.

Patients aged ≥50 years with T1-3, node-positive, hormone receptor-positive, and HER2-negative BC who underwent axillary lymph node dissection (ALND) were retrospectively reviewed at 2 centers. Excluded were those who received neoadjuvant chemotherapy or had bilateral cancers.

The correlation between the number of abnormal axillary nodes detected by ultrasound, demographic and histological parameters, and the number of metastatic nodes found on ALND was examined.

Of the 138 patients included, 59 (42.8%) had 1-3 metastatic nodes, while 79 (57.2%) had >3 metastatic nodes on ALND. Logistic regression and ROC analysis revealed that the number of abnormal nodes detected by ultrasound was significantly predictive (P< 0.001) of limited nodal burden (ROC AUC = 0.7135). Ultrasound cut-offs of 5, 6, and 8 abnormal nodes corresponded to probabilities of <4 metastatic nodes of 0.057, 0.026, and 0.005, respectively, with 100% specificity.

The analysis revealed that a cut-off of ≤5 ultrasound-detected abnormal nodes effectively distinguishes patients with limited from those with high nodal burden, demonstrating high specificity.

Therefore, integrating the number of abnormal ultrasound-detected nodes into clinical practice may aid in decision-making between upfront surgery and gene assay testing or neoadjuvant chemotherapy for this patient cohort. This study received no funding.

Source: https://pubmed.ncbi.nlm.nih.gov/38489166/ 

Lim GH, Allen JC, Lee YS, et al. (2024) “Use of axillary ultrasound to guide breast cancer management in the genomic assay era.” Breast Dis. 2024;43(1):19-23. doi: 10.3233/BD-230032. PMID: 38489166.

Chidamide in HR+/HER2- MBC: Real-world Evidence

KEY TAKEAWAYS

  • The study aimed to assess chidamide’s effectiveness, safety, and treatment patterns while identifying clinicopathological factors predicting its efficacy in real-world settings.
  • Real-world data supported chidamide use in HoR-positive, HER2-negative MBC patients.

Chidamide, a selective histone deacetylase inhibitor, is approved for metastatic breast cancer (MBC) patients with hormone receptor (HoR)-positive and HER2-negative status.

Doudou Li and the team spearheaded a study that aimed to assess chidamide’s efficacy, safety, and treatment patterns while identifying clinicopathological factors predicting its effectiveness in real-world scenarios.

In a multicenter retrospective design, the study enrolled consecutive MBC patients treated with chidamide from January 2020 to August 2021 across 11 institutions. Premenopausal and postmenopausal women with ER-positive, HER2-negative MBC that had been clinically or histologically proven were eligible, as long as they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Multiple primary malignancies or missing baseline characteristics were exclusion criteria. Patients received oral chidamide at 30 mg twice weekly, combined with either aromatase inhibitors (AIs) or non-AIs. Efficacy analyses encompassed progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). Univariate and multivariate Cox regression analyses were conducted to identify potential predictors of efficacy.

About 157 patients were included for analysis, with a median of four prior treatment lines before chidamide. The median PFS for the total population was 4.2 months (95% CI 3.8-4.5). The CBR was 31.3 percent, and the ORR was 7.5%. The effectiveness of chidamide was not affected by individuals receiving different endocrine combinations or those who had previously had treatment with CDK4/6 inhibitors.

According to the multivariate analysis, patients with liver metastases (adjusted HR = 1.66, 95% CI 1.14-2.43, adjusted P = 0.008) or ≥3 prior treatment lines (adjusted HR = 1.80, 95% CI 1.17-2.77, adjusted P = 0.008) showed significantly worse PFS. The most frequent adverse events (AEs) linked to chidamide were anemia, leukopenia, neutropenia, and thrombocytopenia.

Based on real-world evidence, the study indicated that chidamide effectively cures HoR-positive and HER2-negative MBC, especially in patients who have already had treatment with CDK4/6 inhibitors and those undergoing different endocrine combinations.

Research funding was provided by the Beijing Science and Technology Innovation Medical Development Foundation, Chinese Young Breast Experts Research project, and CSCO-ROCHE Cancer Research Fund 2019.

Source: https://pubmed.ncbi.nlm.nih.gov/38457252/ 

Li D, Jin Y, Lin M, et al.(2024) ‘’Treatment patterns and clinical outcomes of chidamide combined with endocrine therapy in hormone receptor-positive, HER2-negative metastatic breast cancer: A real-world multicenter study.’’ Cancer Med. 2024 Feb;13(4):e6762. doi: 10.1002/cam4.6762. PMID: 38457252; PMCID: PMC10923034.

Ribociclib + Letrozole in HR+ Breast Cancer: RIBECCA

KEY TAKEAWAYS

  • The phase 3b RIBECCA study aimed to investigate the real-world efficacy of ribociclib plus letrozole in postmenopausal women with HR+HER2- ABC.
  • The primary endpoint was to determine CBR.
  • Researchers concluded that in this diverse HR+HER2- ABC population, ribociclib plus letrozole demonstrated consistent efficacy and safety, mirroring pivotal trial outcomes.

In MONALEESA-2, combining ribociclib with letrozole demonstrated a substantial increase in progression-free survival (PFS) for postmenopausal women diagnosed with HR+HER2- advanced breast cancer (ABC).

Peter A Fasching and his team aimed to assess the RIBociclib for the treatment of advanCed breast CAncer (RIBECCA) study and its effectiveness of ribociclib plus letrozole in a patient population representative of routine clinical practice.

Researchers conducted an inclusive analysis in a multicenter, open-label, single-arm, phase 3b study. Patients diagnosed with HR+HER2-ABC, deemed ineligible for curative therapy, and possessing an ECOG performance status of ≤ 2, were enrolled. Ribociclib plus letrozole was administered in (cohort A: postmenopausal women and men in first-line; cohort B: pre-/perimenopausal women in first-line [B1], patients pretreated for advanced disease [B2]). 

The primary endpoint focused on clinical benefit rate (CBR) by week 24, with secondary endpoints included overall response rate (ORR), PFS, overall survival (OS), and safety. Multivariable Cox regression analysis explored the association between patient and tumor characteristics with PFS.

About 487 patients were included in the efficacy evaluation, with 502 assessed for safety. By week 24, the CBR reached 60.8% (95% CI, 56.3-65.1), and the ORR was 19.3% (95% CI, 15.9-23.1). Median PFS was 21.8 months (95% CI, 13.9-25.3) for first-line postmenopausal patients and 11.0 months (95% CI, 8.2-16.4) for premenopausal and pretreated patients. The median OS was not reached.

Factors such as higher baseline ECOG performance status, elevated histological grade, and negative progesterone receptor status had an unfavorable impact on PFS. The most common adverse events (AEs) included neutropenia (50.0%), nausea (42.0%), and fatigue (39.2%).

The study concluded that in this diverse population of patients with HR+HER2- ABC, the efficacy and safety outcomes of ribociclib plus letrozole closely mirrored those observed in pivotal trials.

This study was sponsored by Novartis Pharma GmbH, Germany.

Clinical Trial: https://clinicaltrials.gov/study/NCT03096847

Source: https://pubmed.ncbi.nlm.nih.gov/38154393/

Fasching PA, Decker T, Hartkopf A, et.al (2024). Efficacy, safety, and prognosis prediction in patients treated with ribociclib in combination with letrozole: Final results of phase 3b RIBECCA study in hormone receptor positive, human epidermal growth factor receptor-2 negative, locally advanced or metastatic breast cancer. Eur J Cancer. 2024 Feb;198:113480. doi: 10.1016/j.ejca.2023.113480. Epub 2023 Dec 15. PMID: 38154393.

Efficacy & Safety of T-DXd in HER2+ BC

Efficacy & Safety of T-DXd in HER2+ BC

KEY TAKEAWAYS

  • The study aimed to investigate the real-world efficacy and safety of T-DXd in patients with heavily pretreated HER2+ metastatic/unresectable BC.
  • Researchers noticed significant antitumor activity and favorable tolerability of T-DXd.

Early access program (formerly cohort Temporary Authorization for Use) was granted for trastuzumab deruxtecan (T-DXd) based on the DESTINY-Breast01 trial, which demonstrated its efficacy and safety in HER2-positive (+) metastatic/unresectable breast cancer (BC) after ≥2 anti-HER2-based regimens received at a metastatic stage.

Thierry Petit and the team aimed to assess the response to treatment and adverse events associated with T-DXd in patients with BC.

They performed an inclusive analysis within a multicenter real-world early access program, comprising patients with HER2+ metastatic/unresectable BC who had undergone pretreatment with at least 2 lines of anti-HER2 regimens. These patients received T-DXd at a dosage of 5.4 mg/kg intravenously in monotherapy every 3 weeks.

About 459 patients (median age, 58 years; hormone receptor-positive, 67%; brain metastases, 28.1%) were administered T-DXd. Prior to enrollment, 81.7% of patients had undergone radiation therapy, and 76.5% had received surgery. The median number of prior metastatic treatment lines was 4(range, 2-22), with almost all patients (99.8%) having received trastuzumab, 94.8% trastuzumab emtansine, and 79.3% pertuzumab. Follow-up was conducted from September 30, 2020, to March 30, 2021, spanning a median duration of T-DXd treatment of 3.4 (range, 0-7.8) months.

Among 160 patients with available tumor assessment, the objective response rate was 56.7%, with 12.1% experiencing progression. In 57 patients with available brain tumor assessment, complete or partial intracranial response was observed in 35.7% of patients, while 5.4% experienced progression. A total of 17 (3.7%) patients were reported to have interstitial lung disease (ILD), with no ILD-related deaths recorded.

The study concluded that in patients with heavily pretreated HER2+ metastatic/unresectable BC, T-DXd demonstrated significant antitumor activity comparable to that reported in previous clinical studies. Furthermore, T-DXd exhibited favorable tolerability with no new safety signals observed, affirming its potential as a valuable therapeutic option in this challenging clinical setting.

The study was sponsored by AstraZeneca and Daiichi Sankyo.

Source: https://pubmed.ncbi.nlm.nih.gov/38733172/

Petit T, Hajjaji N, Antoine EC, et al. (2024). “Trastuzumab deruxtecan in previously treated HER2-positive metastatic or unresectable breast cancer: Real-life data from the temporary use authorization program in France.” Cancer Med. 2024 May;13(9):e7168. doi: 10.1002/cam4.7168. PMID: 38733172; PMCID: PMC11087844.

HER2-low vs HER2-negative MBC: Improved Survival

KEY TAKEAWAYS

  • The study aimed to investigate features and outcomes of HER2-negative and HER2-low MBC using real-world data.
  • The results demonstrated that the HER2-low tumors were associated with improved survival compared to HER2-negative tumors in MBC.

Investigating real-world data, Zachary Neubauer and the team aimed to analyze characteristics and outcomes of HER2-negative and HER2-low metastatic breast cancers (MBC).

The National Cancer Database was utilized to identify MBC patients classified as HER2-low or HER2-negative via immunohistochemical staining. Demographic and clinical correlates of each subtype were identified through binomial regression analysis. Additionally, survival correlates were identified through Cox multivariable regression analysis (MVA) and propensity-match analysis.

After excluding missing data, 24,636 patients diagnosed with MBC between 2008 and 2015 were identified. Of these, 27.9% were HER2-negative, and 72.1% were HER2-low. No significant demographic differences were observed between the groups. HER2-low tumors were half as likely to exhibit concomitant hormone receptor-positive status (P < 0.01).

Among hormone receptor-negative patients, the 3-year survival rate was 33.8% for HER2-low and 32.2% for HER2-negative (P< 0.05) and among hormone receptor-positive patients, the corresponding rates were 60.9% and 55.6% for HER2-low and HER2-negative cases, respectively ( P< 0.05). HER2-low cases demonstrated improved survival in multivariable regression analysis (HR = 0.95, 95% CI 0.91-0.99) and propensity-matching (HR = 0.92, 95% CI 0.89-0.96).

 In a subset analysis focusing on hormone receptor-positive cases, HER2-low status remained associated with better survival (HR = 0.93, 95% CI 0.89-0.98) in propensity-matched multivariable regression analysis. Correlates of worse survival included older age as a continuous variable (HR = 1.02, 95% CI 1.02-1.02) and Black race (HR = 1.26, 95% CI 1.20-1.32) [all P< 0.01].

This study, the largest analysis conducted to date, revealed a statistically significant association of HER2-low tumors that exhibited improved survival compared to HER2-negative tumors in MBC. No funding was provided for the study.

Source: https://pubmed.ncbi.nlm.nih.gov/38379326/

Neubauer Z, Hasan S, Press RH, et al. (2024) ‘’Prognostic implications of HER2NEU-low in metastatic breast cancer.’’ Cancer Med. 2024 Jan;13(2):e6979. doi: 10.1002/cam4.6979.

Enhanced PFS With Oral SERDs in HER+/HER2- ABC

KEY TAKEAWAYS

  • The study aimed to evaluate the safety of PFS in SERDs in HER+, HER2- aBC pts after progression on ≥ 1 line of ET.
  • The results demonstrated that oral SERD offers significant PFS benefits over standard ET in advanced HER+/HER2- breast cancer pts.

Advanced breast cancer (aBC) with human epidermal growth factor receptor-positive (HER+) and human epidermal growth factor receptor 2-negative (HER2-) status often progresses after initial endocrine therapy (ET). New treatment options are needed.

Oral selective estrogen receptor degraders (SERDs) have emerged as a promising new class of drugs for aBC. Their effectiveness, particularly after progression on ≥ 1 line of ET,  remains a subject of ongoing debate.

Huang X and other members sought to clarify the value of oral SERDs for HER+ and HER2- aBC patients who had progressed on at least one line of ET. They conducted a meta-analysis of clinical trials to assess the impact of SERDs on progression-free survival (PFS) and safety in this specific patient population.

Researchers systematically and comprehensively searched the Cochrane Library, Embase, PubMed, and conference proceedings from SABCS, ASCO, ESMO, and ESMO Breast. To assess the pooled HRs and 95% CIs for treatment with oral SERDs versus standard of care, random or fixed effects models were employed, depending on the data’s characteristics.

About four studies, including 1,290 patients (pts), were incorporated. The HER for PFS indicated that the oral SERD regimen outperformed standard care in patients with HER+/HER2- aBC following progression on at least one line of ET (HR: 0.75, 95% CI: 0.62-0.91, P=0.004).

In patients harboring ESR1 mutations, the oral SERD regimen yielded better PFS than standard care (HR: 0.58, 95% CI: 0.47-0.71, P<0.00001). For patients experiencing disease progression after prior CDK4/6 inhibitor use, a PFS benefit was observed in the oral SERD treatment arms versus standard care (HR: 0.75, 95% CI: 0.64-0.87, P=0.0002).

The results concluded that the oral SERD regimen significantly improved PFS compared to standard ET in patients with HER+/HER2- aBC who had progressed on at least one line of ET. Oral SERDs were preferred for patients with ESR1 mutations and could potentially replace fulvestrant. The oral SERD regimen also offered a PFS benefit in patients who had experienced disease progression after prior CDK4/6 inhibitor use.

No funding was provided for the study.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763362/

Clinical trial: https://www.clinicaltrials.gov/study/NCT03778931

https://clinicaltrials.gov/study/NCT04214288

https://clinicaltrials.gov/study/NCT04059484

https://clinicaltrials.gov/study/NCT04576455

Huang X, Yu Y, Luo S, et al. “The value of oral selective estrogen receptor degraders in patients with HR-positive, HER2-negative advanced breast cancer after progression on ≥ 1 line of endocrine therapy: systematic review and meta-analysis” doi: 10.1186/s12885-023-11722-4. 

 

D-Dimer and Thrombin: Prognostic Score for Breast Cancer

KEY TAKEAWAYS

  • The HYPERCAN study observational trial aimed to investigate the predictive value of prechemotherapy hemostatic biomarkers for high-risk breast cancer pts.
  • Researchers noticed that TG and D-dimer, offer a promising tool for identifying high-risk breast cancer pts prone to early disease recurrence.

Hemostatic biomarkers have garnered attention for their potential in predicting specific cancer outcomes, such as survival, malignant disease recurrence, and progression. Despite promising results from small, single-center studies, the need for confirmatory data from large, prospective studies persists. In this context, the HYPERCAN study was initiated, focusing on a substantial cohort of high-risk breast cancer patients (pts).

Patricia Gomez-Rosas and her team aimed to investigate whether prechemotherapy hemostatic levels could serve as predictive indicators for disease recurrence (DR). The objective was to assess and generate an internally validated risk assessment model based on pre-treatment values of thrombin generation (TG) and D-dimer. This model aimed to identify subjects at higher risk of DR within the initial 2 years post tumor resection.

The HYPERCAN study conducted an inclusive analysis as part of its prospective, observational, multicenter design. Specifically focused on evaluating hemostatic biomarkers, the study aimed to elucidate their correlation with disease recurrence, disease progression, mortality response to therapy, and thrombosis in pts diagnosed with surgically resected high-risk breast cancer. The analysis encompassed pts enrolled between 2012 and 2019.

The study performed an extensive examination of blood samples collected at enrollment, prior to the initiation of anticancer treatment. TG was assessed using both the ST-Genesia system (STG-ThromboScreen reagent, with and without thrombomodulin) and the calibrated automated thrombogram (CAT) at 5 pM TF. Additionally, D-dimer, fibrinogen, prothrombin fragment 1+2 (F1+2), and proteins C and free protein S (FPS) were measured.

The primary outcome under scrutiny was early-DR (E-DR) within a 2-year timeframe. 

About 1,059 pts, with a gender distribution of 15 males and 1,044 females, and a mean age of 53 years (SD±11), were included in the analysis. Surgical procedures comprised breast-conserving resection in 53% of cases and mastectomy in 47% pts. HER-2 expression was positive in 26% of tumor specimens. Predominant molecular subtypes were Luminal B HER2 negative (32%), Luminal A (22%), Luminal B HER2 positive (19%), Triple-negative (13%), and HER2 positive (8%). The majority of tumors (86%) were classified as invasive ductal carcinoma.

All pts were eligible for systemic adjuvant chemotherapy, and those with HER-2 positivity were candidates for trastuzumab. Within 2 years from enrollment, 53 pts (5.5%) experienced early disease recurrence (E-DR), 8 died, and 92 were lost at follow-up. E-DR pts exhibited worse stage (IIIC), a higher frequency of triple-negative subtype, and less often Luminal-B/HER2-positive molecular subtypes (p<0.05).

Furthermore, E-DR subjects demonstrated elevated pre-chemotherapy levels of D-dimer (p=0.004) and peak TG measured by both Genesia (p=0.001) with and without thrombomodulin, as well as CAT assays (p<0.001). Other coagulation parameters did not significantly differ between the two groups.

A competitive multivariable proportional hazard regression model, adjusted for age and surgery status, identified D-dimer and TG peak (by both methods) as independent risk factors for E-DR. Internal validation through 1,000-bootstrapping resampling confirmed the robustness of the model. A continuous risk score incorporating D-dimer and TG achieved a ROC AUC of 0.652 (p<0.001). This risk score effectively stratified pts into high- and low-risk categories for E-DR (HR 23 vs 0%: Log-rank <0.001).

The study concluded that a validated risk model, utilizing pre-treatment TG and D-dimer values, effectively identifies high-risk breast cancer pts for early disease recurrence. If externally validated, this score could enhance clinical surveillance and guide treatment decisions, preventing overtreatment in low-risk individuals.

The study is sponsored by A.O. Ospedale Papa Giovanni XXIII

Source: https://ashpublications.org/blood/article/142/Supplement%201/5460/505075/A-D-Dimer-and-Thrombin-Generation-Based-Risk-Score

Clinical Trial: https://clinicaltrials.gov/study/NCT02622815

Rosas P G, Marchetti M, Giaccherini C, et al. (2023). “A D-Dimer and Thrombin Generation-Based Risk Score Predicts Early-Disease Recurrence in a Prospective Cohort of 1,059 High-Risk Breast Cancer Patients.” Presented at ASH 2023.

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