CDK4/6 Inhibitors: Paving the Way for HR-Positive, HER2-Negative Early Breast Cancer

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Kristi Orbaugh, RN, MSN, RNP, AOCN ◽  
Val R. Adams, PharmD, FCCP, BCOP, FHOPA ◽  
Theresa W. Gillespie, PhD, MA, RN, FAAN
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Free Survival ◽  
Her2 Breast Cancer ◽  
Oral Agents

Cyclin-dependent kinase (CDK) 4/6 inhibitors are revolutionizing care for patients with advanced and metastatic hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2–) breast cancer. These oral agents, often combined with other hormone-based therapy, have demonstrated considerable success in clinical trials and are used widely in oncology practices. CDK4/6 inhibitors are also being investigated for the treatment of early stage HR+, HER2– breast cancer. The addition of abemaciclib to adjuvant endocrine therapy improved invasive disease-free survival and distant relapse-free survival compared with endocrine therapy alone in patients with HR+, HER2–, node-positive, high-risk early breast cancer, and is now FDA-approved as adjuvant treatment in this setting. Here we review recent clinical data supporting the use of CDK4/6 inhibitors in both early and metastatic breast cancer. In addition, an expert faculty panel will discuss practical strategies to promote and improve adherence and side effect management in patients being treated with oral CDK4/6 inhibitors.

Clinical response at 4 months to neoadjuvant letrozole predicts distant disease free survival in postmenopausal women with stage II-III ER/PgR-positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10531-10531 ◽  
Author(s):  
V. Guillem ◽  
A. Llombart-Cussac ◽  
J. Lopez Guerrero ◽  
A. Guerrero ◽  
C. Fuster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Response ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Prognostic Indicators ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free

10531 Background: Letrozole (L) is more active than tamoxifen in early stage ER[+] breast cancer both as adjuvant (BIG-98 trial) or neoadjuvant (LET-024) therapy. However, complete pathological remissions to neoadjuvant endocrine therapy are anecdotal (<5%), there are no new prognostic indicators with clinical implications. Methods: We have review our series of postmenopausal patients with stage II-III breast cancer ER/PgR[+] breast cancer treated in our institution with L as neoadjuvant therapy. All patients had completed 4 months of therapy (in the absence of PD), and had measurable clinical (or radiological) disease. An independent statistical analysis was conducted for disease free (DFS) and distant disease free survival (DDFS). Results: From IV/99 to XII/04, 107 patients fulfill the criteria. Median age 76 years (range 64 to 92); median tumour size 35 mm (range 25 to 100); cT2 75 (70%), cT3/4 32 (30%); cN[-] 83 (78%). The ORR (PR + CR) at 4 months was 63% (7 CR and 60 PR), 4 patients had PD as best response (4%) and 36 a SD (34%). Surgery was done in 63 patients (59%), including all non-responders. Only 2 patients received adjuvant CT. With a median follow-up of 32 month (range 8 to 66), 12 patients had relapsed (9 distant). The 3 years DFS and DDFS were 84% and 90% respectively. In univaried analysis: cN (p < 0.02), cT3/4 (p < 0.02), and clinical response at 4 months (CR) (p = 0.003) were related to DFS; and HER2 (p < 0.05), cN (p < 0.003), and CR (p = 0.007) with DDFS. Other factors like cT, HR-levels, or surgery were not significant. Multivariate analysis showed that only OR and cN remained independently predictive both for DFS and DDFS. Conclusions: Clinical response to neoadjuvant letrozole therapy is an independent predictor of distant disease free survival and could be of value to recommend or deny more aggressive therapies in addition to endocrine therapy. [Table: see text] No significant financial relationships to disclose.

Generation of adaptive HER2-specific immunity in HER2 breast cancer patients by addition of trastuzumab to chemotherapy in the adjuvant setting: NCCTG (Alliance) study N9831.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 522-522 ◽  
Author(s):  
Keith L. Knutson ◽  
Edith A. Perez ◽  
Karla V. Ballman ◽  
Courtney L. Erskine ◽  
Nicholas Fox ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Breast Cancer Patients ◽  
Adjuvant Setting ◽  
Free Survival ◽  
Specific Immunity ◽  
Her2 Breast Cancer ◽  
Disease Free

522 Background: In the adjuvant setting, patients with HER2 breast cancer treated with trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induces HER2-specific antibodies which correlate with response to therapy in patients with HER2+ metastatic breast cancer. It remained unclear from those studies, however, whether the HER2-specific immunity played a role and if antibody immunity was associated with improved disease free survival in the adjuvant setting. In the present study, we addressed these questions by analyzing sera samples from a subset of patients enrolled in the NCCTG adjuvant trial, N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. Methods: Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831 (22 Arm A; 14 Arm B, and 14 Arm C). Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and presented as an index (>0.2 was considered a positive response). Results: Prior to therapy, across all three arms, N9831 patients had similar mean HER2 IgG levels (0.19 units in Arm A, 0.14 in Arm B, and 0.23 in Arm C, P=0.85). Following treatment, the mean levels of antibodies increased in Arm B to 0.35 units and in Arm C to 0.56 units and were higher (p<0.001) than in Arm A where levels did not increase. The proportion of patients who demonstrated antibody immunity increased by 9% in Arm A, 50% in Arm B and 28% in Arm C (P=0.026). Although the event rate was low in this cohort, Cox modeling suggested that larger increases in antibodies were associated with improved disease free survival (HR=0.23; p=0.04). Conclusions: These results show that the increased antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant and results from the inclusion of trastuzumab. The findings may have important implications for improving treatment outcomes in patients treated with trastuzumab.

scholarly journals Validation of the GenesWell BCT Score in Young Asian Women With HR+/HER2− Early Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Mi Jeong Kwon ◽  
Jai Min Ryu ◽  
Soo Youn Cho ◽  
Seok Jin Nam ◽  
Seok Won Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Predictive Value ◽  
Age Groups ◽  
Young Patients ◽  
Disease Free Survival ◽  
Low Risk ◽  
Tissue Samples ◽  
Free Survival ◽  
Her2 Breast Cancer

BackgroundThe prognostic or predictive value of commonly used multigene assays in young patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer is unclear. In this study, we assessed the prognostic value of the GenesWell BCT assay according to age group.MethodsWe identified patients with pN0-1, HR+/HER2− breast cancer in a prospective cohort of women who underwent surgery between 2005 and 2017. The GenesWell BCT assay was performed on tissue samples from selected patients. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were compared between the risk groups assigned by the BCT score.ResultsA total of 712 patients were eligible for analysis. The median follow-up time was 7.47 years. The BCT score was prognostic in patients aged ≤50 years (n = 404) and those aged &gt;50 years (n = 308). In both age groups, the 10-year DMFS and DFS rates for patients classified as high risk by the BCT score were significantly lower than those for patients classified as low risk. A multivariate analysis revealed that the BCT score was an independent prognostic factor for DFS in patients aged ≤50 years (hazard ratio, 1.28; 95% CI, 1.05–1.56; P = 0.015), as well as those aged &gt;50 years.ConclusionThe BCT score could be used to identify low-risk patients who will not benefit from adjuvant chemotherapy to treat HR+/HER2− early breast cancer regardless of age. A further prospective study to assess the prognostic and predictive value of the BCT score is required.

scholarly journals Management of Early-Stage Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

2021 ◽  
Vol 17 (6) ◽  
pp. 320-330 ◽  
Author(s):  
Sonia Pernas ◽  
Sara M. Tolaney
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Epidermal Growth ◽  
Positive Breast Cancer

The addition of trastuzumab to chemotherapy dramatically improved the prognosis of early-stage human epidermal growth factor receptor 2 (HER2)–positive breast cancer. However, 15%-31% of patients still develop disease recurrence, on the basis of long-term follow-up of adjuvant pivotal trials. A better understanding of tumor biology has led to the development of optimized anti-HER2 drugs and add-on strategies to further improve survival outcomes. In the neoadjuvant setting, dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy has increased the rate of pathologic complete response, a surrogate marker of improved long-term outcome; yet, in the adjuvant setting, it has led to small benefits in invasive disease-free survival. Extended adjuvant therapy with the irreversible pan-HER2 inhibitor neratinib is an option for selected patients with HER2-positive and estrogen receptor–positive disease who have received neoadjuvant or adjuvant chemotherapy plus trastuzumab. Additionally, the use of the antibody-drug conjugate trastuzumab-emtansine has led to a significant improvement in invasive disease-free survival for patients with residual disease following neoadjuvant therapy and has taught us the importance of using preoperative therapy to adapt adjuvant treatment. Nevertheless, recurrences in the brain remain an important caveat, and not all patients benefit to the same extent from anti-HER2 therapies. Biologic heterogeneity within HER2-positive disease may modulate treatment response and prognosis. De-escalating treatment strategies to avoid unnecessary treatments and toxicities, without compromising outcomes, have become a crucial focus of research. To stratify patient risks and optimize treatment selection, other biomarkers including intrinsic subtype, level of HER2, and tumor-infiltrating lymphocytes should be further evaluated. We discuss the latest evidence on the current approach of early-stage, HER2-positive breast cancer and present future perspectives on its management.

Invasive disease-free survival benefit following neratinib as extended adjuvant therapy in centrally-confirmed HER2+ early-stage breast cancer: The ExteNET phase III randomized placebo-controlled trial.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 117-117 ◽  
Author(s):  
Arlene Chan ◽  
Miguel Martin ◽  
Gunter Von Minckwitz ◽  
Bent Ejlertsen ◽  
Stephen K. L. Chia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Invasive Disease ◽  
Phase Iii ◽  
Free Survival ◽  
Disease Free

117 Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor with clinical efficacy in trastuzumab pre-treated HER2-positive (HER2+) metastatic breast cancer (BC). ExteNET is an ongoing multicenter randomized placebo-controlled phase III trial evaluating the efficacy and safety of a 1-year course of neratinib in patients with early-stage HER2+ BC after trastuzumab-based adjuvant therapy (clinicaltrials.gov: NCT00878709). Methods: Women with locally-confirmed early-stage HER2+ BC were randomly assigned to oral neratinib 240mg/day or matching placebo for 1 year. Archived diagnostic tumor samples were submitted for HER2 gene amplification testing at a central laboratory. Primary endpoint: invasive disease-free survival (iDFS). Secondary endpoints: DFS including ductal carcinoma in situ (DFS+DCIS); distant disease-free survival (DDFS); time to distant recurrence (TDR). Stratified Cox proportional-hazards models were used to estimate hazard ratios (HR) for the ITT and amended ITT (aITT) populations; unstratified models were used for the centrally confirmed HER2 population. Treatment groups were compared using 2-sided log-rank tests. Results: The ITT population included 2840 patients (neratinib, N=1420; placebo, N=1420). The higher-risk aITT population (i.e. node-positive disease and randomized ≤1 year of completing prior trastuzumab) included 1873 patients (neratinib, N=938; placebo, N=935). Of the tumor samples analyzed, 1463 (86%) were centrally confirmed (neratinib, N=741; placebo, N=722). Conclusions: Neratinib significantly improves iDFS in trastuzumab-treated early-stage HER2+ BC patients. An enhanced treatment effect is observed with neratinib in women with centrally confirmed HER2+ tumors. Clinical trial information: NCT00878709. [Table: see text]

scholarly journals Top 3 abstracts concerning hormone-receptor-positive early breast cancer

2021 ◽  
Author(s):  
Simon Peter Gampenrieder ◽  
Gabriel Rinnerthaler ◽  
Richard Greil
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Hormone Receptor ◽  
Menopausal Status ◽  
Pathologic Complete Response ◽  
Oncotype Dx ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer

SummaryThe three top abstracts at the 2020 virtual San Antonio Breast Cancer Symposium regarding hormone-receptor-positive early breast cancer, from our point of view, were the long-awaited results from PenelopeB and RxPONDER as well as the data from the ADAPT trial of the West German Study Group. PenelopeB failed to show any benefit by adjuvant palbociclib when added to standard endocrine therapy in patients without pathologic complete response after neoadjuvant chemotherapy. RxPONDER demonstrated that postmenopausal patients with early hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2−) breast cancer, 1–3 positive lymph nodes and an Oncotype DX Recurrence Score of less than 26 can safely be treated with endocrine therapy alone. In contrast, in premenopausal women with positive nodes, adjuvant chemotherapy plays still a role even in case of low genomic risk. Whether the benefit by chemotherapy is mainly an indirect endocrine effect and if ovarian function suppression would be similarly effective, is still a matter of debate. The HR+/HER2− part of the ADAPT umbrella trial investigated the role of a Ki-67 response to a short endocrine therapy before surgery in addition to Oncotype DX—performed on the pretreatment biopsy—to identify low-risk patients who can safely forgo adjuvant chemotherapy irrespective of menopausal status.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

Sign in / Sign up

Export Citation Format

Share Document