De-escalation of adjuvant chemotherapy for HER2 negative breast cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Okines DAF
PROVIDER: S-EPMC8315337 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Patients with high-risk non-metastatic breast cancer are recommended for chemotherapy, preferably in the neoadjuvant setting. Beyond advantages such as a better operability and an improved assessment of individual prognosis, the preoperative administration of systemic treatment offers the unique possibility of selecting postoperative therapies according to tumor response. In patients with HER2-positive disease, both the escalation of therapy in the case of high-risk features and the de-escalation in patients with a low tumor load are currently discussed. Patients with small node-negative tumors receive primary surgery and, upon confirmation of pathological T1 N0 status, de-escalated adjuvant therapy with paclitaxel and trastuzumab. For those with a large tumor and/or nodal involvement, neoadjuvant polychemotherapy with a dual antibody blockade is recommended. Patients with invasive residual disease benefit from switching postoperative therapy to the antibody-drug-conjugate trastuzumab emtansine (T-DM1). In this review, we discuss current evidence and controversies regarding post-neoadjuvant treatment strategies in HER2-positive breast cancer.
| S-EPMC9221124 | biostudies-literature
Project description:In the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02-4.51, p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06-1.68, p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00-2.22, p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07-1.64, p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23-6.02, p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.
| S-EPMC7994398 | biostudies-literature
Project description:BackgroundGiven excellent survival outcomes in breast cancer, there is interest in de-escalating the amount of chemotherapy delivered to patients. This approach may be of even greater importance in the setting of the COVID-19 pandemic.MethodsThis concurrent mixed methods study included (1) interviews with patients and patient advocates and (2) a cross-sectional survey of women with breast cancer served by a charitable nonprofit organization. Questions evaluated interest in de-escalation trial participation, perceived barriers/facilitators to participation, and language describing de-escalation.ResultsSixteen patient advocates and 24 patients were interviewed. Key barriers to de-escalation included fear of recurrence, worry about decision regret, lack of clinical trial interest, and dislike for focus on less treatment. Facilitators included trust in physician recommendation, toxicity avoidance, monitoring for progression, perception of good prognosis, and impact on daily life. Participants reported that the COVID-19 pandemic made them more likely to avoid chemotherapy if possible. Of 91 survey respondents, many (43%) patients would have been unwilling to participation in a de-escalation clinical trial. The most commonly reported barrier to participation was fear of recurrence (85%). Few patients (19%) considered clinical trials themselves as a barrier to de-escalation trial participation. The most popular terminology describing chemotherapy de-escalation was "lowest effective chemotherapy dose" (53%); no patients preferred the term "de-escalation."ConclusionsFear of recurrence is a common concern among breast cancer survivors and patient advocates, contributing to resistance to de-escalation clinical trial participation. Additional research is needed to understand how to engage patients in de-escalation trials.
| S-EPMC8124110 | biostudies-literature
Project description:Long-term outcomes in breast cancer patients differ based on the molecular subtype, with HER2-E being the most aggressive one. Advances in clinical practice have dramatically shifted HER2+ breast cancer prognosis. Risk adapted strategies to individualize therapies are necessary. De-escalation approaches have been encouraged based on the risks of clinical-pathological factors. Molecular gene subtyping could further accurately define HER2 addicted tumours that are sensitive to anti-HER2 therapies, thus sparing unnecessary treatments. The transition from immunochemistry to molecular profiling in HER2+ breast cancer is discussed.
| S-EPMC8833556 | biostudies-literature
Project description:BackgroundPatients with luminal HER2-negative tumours have a favourable prognosis. However, there is a subpopulation in which poorer outcomes are obtained with endocrine therapy alone. This subpopulation is considered to benefit from chemotherapy. However, the significance of chemotherapy for those with luminal tumours has decreased due to recent changes in treatment strategies. Thus, it is often difficult to determine whether we should recommend chemotherapy to such patients in clinical practice. We investigated Ki67 expression, as a means of predicting the responses of luminal HER2-negative breast cancer patients to neo-adjuvant chemotherapy (NAC), in order to identify a subpopulation that would benefit from these treatments.MethodsWe enrolled 114 luminal HER2-negative breast cancer patients undergoing surgery after NAC. Biomarkers were examined using biopsy specimens obtained prior to treatment, to avoid any chemotherapy-related effects. Chemotherapy effects were determined employing operative specimens and we defined pathological complete response (pCR) as invasive nest disappearance, based only on the primary breast tumour. We applied receiver operating characteristic curve analysis to data from our 114 patients, to investigate Ki67 expression as a predictor of pCR.ResultsThe pCR rate was significantly higher for tumours with high Ki67 expression (p < 0.01) and all patients who obtained pCR remained recurrence-free during the median 58-month observation period. We identified 35% as the Ki67 cut-off value which distinguishes those with a pCR from other cases. Another dataset, comprised of 196 patients with a median 29-month observation period, was recruited for validation. Disease-free survival was found to be significantly (p < 0.01) lower in the patients with tumours in which Ki67 expression was higher than 35%.ConclusionOur results raise the possibility of the luminal HER2-negative subpopulation with Ki67 expression higher than 35% benefiting from chemotherapy, as evidenced by improved survival.
| S-EPMC4124146 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) represents a heterogeneous breast cancer subtype with a poor prognosis. The optimal adjuvant chemotherapy regimen is still unknown. Although numerous large randomized trials have established the benefit of adjuvant anthracyclines and/or taxanes in TNBC, there is no preferred regimen for these patients. There is currently no guideline. Moreover, without knowing the optimal treatment backbone, it will not be possible to evaluate whether adding agents such as platinum or other novel therapies is beneficial for TNBC patients. Furthermore, the best duration of adjuvant treatment in TNBC is still unknown. This review will focus on results of clinical trials that analyzed the benefits of extending the duration of adjuvant treatment in TNBCs with maintenance treatments. We will further discuss promising results in favor of other new agents including capecitabine, metronomic treatment, and biological drugs.
| S-EPMC5527164 | biostudies-other
Project description:BackgroundAdjuvant chemotherapy is a major adjuvant treatment modality for hormonal receptor (HR)-positive and HER2-negative early breast cancer, but only 2%-20% of patients derive practical benefits. How to balance its potential benefits and risks becomes a challenging clinical problem. The purpose of this study was to assess whether RecurIndex assay could serve as an aid for adjuvant chemotherapy decisions in Chinese patients with HR-positive HER2-negative early breast cancer.MethodsThe tissue samples of pT1-2N0 HR-positive HER2-negative breast cancer from multiple centers were detected using RecurIndex assay, based on which the patients were assigned into low- and high-risk groups. The survival outcomes of low- and high-risk patients including those with and without adjuvant chemotherapy were compared, and the risk factors for recurrence and metastasis were identified.ResultsTotally 445 patients were eligible for analysis. By contrast to high-risk patients, low-risk patients represented better 7-year recurrence-free survival (RFS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS) rates. For low-risk patients, no significant differences were shown between those with and without adjuvant chemotherapy in 7-year RFS, DRFS and LRFS rates. These differences were also inapparent between high-risk patients with and without adjuvant chemotherapy. The multivariate model revealed high-risk patients had a significantly elevated risk of recurrence and metastasis than those at low risk.ConclusionHR-positive HER2-negative early breast cancer patients at low risk stratified by RecurIndex assay might be exempt from adjuvant chemotherapy. Whether adjuvant chemotherapy may derive survival benefits for high-risk patients still needs larger cohorts to verify.
| S-EPMC9769189 | biostudies-literature
Project description:BackgroundNo single standard treatment exists for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancers, because most of these patients have been ineligible for the pivotal trials of adjuvant trastuzumab.MethodsWe performed an uncontrolled, single-group, multicenter, investigator-initiated study of adjuvant paclitaxel and trastuzumab in 406 patients with tumors measuring up to 3 cm in greatest dimension. Patients received weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy. The primary end point was survival free from invasive disease.ResultsThe median follow-up period was 4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95% confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due to distant metastatic breast cancer. Excluding contralateral HER2-negative breast cancers and nonbreast cancers, 7 disease-specific events were noted. A total of 13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3 neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to 1.8), both of whom had normalization of the left ventricular ejection fraction after discontinuation of trastuzumab. A total of 13 patients had significant asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined by the study, but 11 of these patients were able to resume trastuzumab therapy after a brief interruption.ConclusionsAmong women with predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2%; 6% of patients withdrew from the study because of protocol-specified adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT00542451.).
| S-EPMC4313867 | biostudies-literature
Project description: Not available
| S-EPMC8866473 | biostudies-literature
Project description:Purpose of reviewDe-escalation of surgery has been central in the evolution of multidisciplinary management of breast cancer. Advances in oncology and increasing use of neoadjuvant chemotherapy (NACT) have opened opportunities for further surgical de-escalation especially for HER2 + and triple negative (TN) disease. The aim of this review is to discuss the recent data on de-escalation of surgery as well as the future directions.Recent findingsPatients with TN and HER2 + breast cancer with excellent response to NACT would be the ideal candidates for surgical de-escalation. Post-NACT image-guided biopsy, potentially combined with machine learning algorithms, may accurately identify patients achieving pathologic complete response that would be eligible for clinical trials assessing safety of omission of breast and axillary surgery.SummaryMultidisciplinary research is required to further support results of preliminary studies. Current data point towards a future when even less or no surgery may be required for exceptional responders.
| S-EPMC9328618 | biostudies-literature