scholarly journals Does trastuzumab-related cardiotoxicity influence long-term outcome in patients with HER-2 positive breast cancer? A prospective study

2021 ◽  
Author(s):  
Grzegorz Piotrowski ◽  
Maciej Kulig ◽  
Arkadiusz Stasiak ◽  
Joanna Stasiak ◽  
Maciej Banach
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Treatment Discontinuation ◽  
Cardiac Complications ◽  
Adjuvant Setting ◽  
Long Term Outcome ◽  
Trastuzumab Treatment ◽  
Her 2 ◽  
Risk Of Cancer ◽  
Positive Breast Cancer

IntroductionTrastuzumab is a monoclonal antibody directed against the HER-2 receptor that has led, in an adjuvant setting, to higher disease-free (DFS) and overall survival (OS) in HER-2 positive breast cancer (BC) compared with chemotherapy alone. Cardiotoxicity often results in early discontinuation of trastuzumab, which may elevate the risk of cancer recurrence or mortality. Our study aimed to assess how early interruption or early permanent termination of adjuvant trastuzumab treatment influences DFS and OS of patients with HER-2 positive BC.Material and methodsThis is a prospective observation of 253 women (55 ±10 years of age) with HER-2 positive unilateral, non-metastatic BC treated with trastuzumab in an adjuvant setting. To monitor the safety of the treatment echocardiography was performed at baseline and every 3 months up to 12 months after the end of therapy. If cardiotoxicity developed, trastuzumab was stopped early. Overall survival and DFS were assessed.ResultsTrastuzumab-associated cardiac complications resulting in treatment discontinuation developed in 52 (20.55%) patients. Median DFS time was 21.1 months in the group with interruption compared with 25.7 months in the group with full trastuzumab treatment, being significantly shorter (HR = 2.32, 95% CI: 1.15–4.71, p = 0.0106). Two year OS in the interruption and no-interruption groups were 80.8% and 88.5%, respectively, which were not statistically significantly different (p = 0.268). In a multivariate regression analysis the cumulative dose of anthracycline (OR = 1.01, 95% CI: 1.00–1.01, p = 0.002) and LVEF at baseline (OR = 0.83, 95% CI: 0.70–0.99, p = 0.0344) were independent predictors of a cardiotoxic effect.ConclusionsTrastuzumab-related cardiotoxicity resulting in early treatment discontinuation negatively influences DFS, but does not seem to influence OS.

scholarly journals Are mutations in K-RAS, BRAF and PIK3CA genes critical for response to adjuvant trastuzumab treatment in patients with HER-2 positive breast cancer?

2014 ◽  
Vol 3 (1) ◽  
pp. 3 ◽  
Author(s):  
Anne Marie Bak Jylling ◽  
Anders Aamann Rasmussen ◽  
Erik Hugger Jakobsen ◽  
René dePont Christensen ◽  
Flemming Brandt Sørensen
Keyword(s):  
Breast Cancer ◽  
Adjuvant Trastuzumab ◽  
Trastuzumab Treatment ◽  
Her 2 ◽  
Positive Breast Cancer

HER-2/neu oncogene protein and prognosis in breast cancer.

1989 ◽  
Vol 7 (8) ◽  
pp. 1120-1128 ◽  
Author(s):  
A K Tandon ◽  
G M Clark ◽  
G C Chamness ◽  
A Ullrich ◽  
W L McGuire
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Node Negative ◽  
Node Positive ◽  
Her 2 ◽  
Neu Oncogene ◽  
Disease Free ◽  
Oncogene Protein ◽  
Positive Breast Cancer

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.

Trastuzumab Beyond Progression in Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: A German Breast Group 26/Breast International Group 03-05 Study

2009 ◽  
Vol 27 (12) ◽  
pp. 1999-2006 ◽  
Author(s):  
Gunter von Minckwitz ◽  
Andreas du Bois ◽  
Marcus Schmidt ◽  
Nicolai Maass ◽  
Tanja Cufer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Time To Progression ◽  
Breast International Group ◽  
International Group ◽  
Trastuzumab Treatment ◽  
Her 2 ◽  
Epidermal Growth ◽  
Breast Group ◽  
Positive Breast Cancer

Purpose Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)–positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression. Methods Patients with HER-2–positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m2 body-surface area on days 1 through 14 [1,250 mg/m2 semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles. The primary end point was time to progression. Results We randomly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab. Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15.6 months of follow-up. Median times to progression were 5.6 months in the capecitabine group and 8.2 months in the capecitabine-plus-trastuzumab group with an unadjusted hazard ratio of 0.69 (95% CI, 0.48 to 0.97; two-sided log-rank P = .0338). Overall survival rates were 20.4 months (95% CI, 17.8 to 24.7) in the capecitabine group and 25.5 months (95% CI, 19.0 to 30.7) in the capecitabine-plus-trastuzumab group (P = .257). Overall response rates were 27.0% with capecitabine and 48.1% with capecitabine plus trastuzumab (odds ratio, 2.50; P = .0115). Continuation of trastuzumab beyond progression was not associated with increased toxicity. Conclusion Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2–positive breast cancer who experienced progression during trastuzumab treatment.

scholarly journals NCMP-03. INTRATHECAL TRASTUZUMAB TREATMENT OF HER-2 POSITIVE LEPTOMENINGEAL BREAST CANCER: THE UNIVERSITY OF MICHIGAN EXPERIENCE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii123-ii123
Author(s):  
Kelsey Peters ◽  
Lindsay Robell ◽  
Aki Morikawa ◽  
Yoshie Umemura ◽  
Yilun Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Treatment Group ◽  
Control Group ◽  
University Of Michigan ◽  
Breast Cancer Patients ◽  
Whole Brain Radiation ◽  
Her 2 ◽  
The University ◽  
Positive Breast Cancer

Abstract PURPOSE Breast cancer is the most common solid tumor to metastasize to the leptomeninges, affecting up to 5% of breast cancer patients. Overall survival for patients with leptomeningeal metastases (LM) is poor, with median survival of 4–6 months following diagnosis. There is limited data available on the efficacy of intrathecal (IT) trastuzumab in the treatment of Her-2 positive LM. METHODS A total of 30 patients with Her-2 positive breast cancer with LM treated at the University of Michigan from 2008–2020 were identified retrospectively. Of these, 13 patients were treated with IT trastuzumab beginning in June 2010 and followed through April 2020. Initial dose was 50–80 mg twice weekly for a minimum of 4 weeks, followed by slow taper. The 17 patients with Her-2 positive breast cancer with LM who did not receive IT trastuzumab served as control. RESULTS The median age of patients in the treatment group was 42 and 52 in the control group. Whole brain radiation therapy was received by 92% of patients in the treatment group and 76% in the control group. The median overall survival from diagnosis of LM to death was 20 months (interquartile range [IQR] 13–60 months) in the treatment group and 6 months (IQR 2–17 months) in the control group. Survival at 3 years and 5 years was 40% and 13%, respectively for the treatment group and 8% and 0% (no data available at 60 months), for the control group. Hazard ratio for death with IT trastuzumab 0.38 (95% CI 0.16–0.91, p=0.024). IT trastuzumab was overall well-tolerated (one patient developed meningitis, while another had shunt malfunction necessitating removal of the reservoir). CONCLUSIONS Patients with HER2+ LM who received IT trastuzumab demonstrated significantly improved OS compared to control with minimal toxicity.

Treatment outcomes among human epidermal growth factor receptor 2 positive breast cancer patients: A systematic review

2021 ◽  
pp. 107815522110055
Author(s):  
Amsalu Degu ◽  
Asha Yussuf
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Treatment Outcomes ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Her 2 ◽  
Positive Breast Cancer

Background The incidence of human epidermal growth factor receptor 2 (HER 2) positive breast cancers is rapidly rising worldwide. Although there have been many studies on HER 2 breast cancer treatment and management in recent years, there is a lack of comprehensive reports on the treatment outcomes and disparities within the available literature. Hence, this review aimed to determine the treatment outcomes and their associated factors among patients with HER2-positive breast cancer. Methods A computer-based systematic literature search was conducted using PubMed, EMBASE, and Google scholar databases of articles published from 2000 to 2020. The following key terms (HER 2 positive breast cancer, predictor, determinant, associated factor) and Medical Subject Headings (MeSH) terms (breast neoplasms, treatment outcome, and risk factors) were used to search the English language published articles. Results In most studies, trastuzumab was the most commonly used treatment regimen used in combination with chemotherapeutic agents. Generally, most of the studies (15 studies) showed that the overall survival outcome was relatively higher after treatment among HER2 positive breast cancer patients. Nonetheless, two studies showed that the absence of significant change in the overall survival despite adequate treatment was given to the study participants. In addition, three studies demonstrated a partial response after treating HER2-positive breast cancer patients. Conclusion Generally, the overall survival outcome was relatively higher after treatment among HER2 positive breast cancer patients. The addition of trastuzumab in most of the studies has shown improvement in the overall survival and the disease-free survival rate of the study patients.

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