Targeted therapy in the treatment of HER-2 positive breast cancer with brain metastases

Metastatic damage to the brain is a frequent manifestation in tumors of various localizations, including breast cancer. Until recently, systemic therapy of metastatic brain damage was of limited use; however, with the advent of targeted drugs that are better understood in terms of the specific molecular targets and biological characteristics of metastases, it is now possible to improve treatment results. In an analysis of the results of studies on the problem of metastasis of breast cancer in the brain, a comparison of the use of various targeted drugs in the treatment of metastatic HER2 + breast cancer is presented. The results of a comparison of the degrees of effectiveness of targeted drugs, both in monotherapy and in combination with chemotherapy, were obtained and analyzed.

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Outcome of Brain Metastases From HER 2–Positive Breast Cancer: Difference in Survival Benefit From Anti-HER 2 Treatment After WBRT With Regard to Prior Targeted Therapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2014.05.870 ◽

2014 ◽

Vol 90 (1) ◽

pp. S247 ◽

Cited By ~ 5

Author(s):

J. Chen ◽

Q. Zhang ◽

X. Yu ◽

Z. Zhang ◽

X. Guo

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Brain Metastases ◽

Survival Benefit ◽

Her 2 ◽

Positive Breast Cancer

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Role of targeted therapy in the treatment of HER-2-positive breast cancer brain metastases

Tumors of female reproductive system ◽

10.17650/1994-4098-2016-12-1-46-51 ◽

2016 ◽

Vol 12 (1) ◽

pp. 46-51

Author(s):

G. A. Dashyan ◽

V. F. Semiglazov ◽

P. V. Krivorot’ko ◽

T. Yu. Semiglazova ◽

E. E. Topuzov ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Brain Metastases ◽

Her 2 ◽

Breast Cancer Brain Metastases ◽

Positive Breast Cancer

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Targeted Therapy of Her-2 Positive Breast Cancer: Past and Future (Preprint)

10.2196/preprints.20451 ◽

2020 ◽

Author(s):

Xue-Fei Wang ◽

Guo-Chao Zhang ◽

Qiang Sun

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Targeted Therapy ◽

Pairwise Comparison ◽

Research Direction ◽

New Drugs ◽

Breast Cancer Patients ◽

Existing Problems ◽

Her 2 ◽

Positive Breast Cancer

BACKGROUND In recent years, with the scientific and technological progress, new drugs for breast cancer have been developed constantly, and the OS and DFS of breast cancer patients are also improving. However, the large number of drugs has also made the clinical trials of drugs disordered. OBJECTIVE To overcome the existing problems in targeted therapy and figure out the best choice of targeted therapy. METHODS we proposed the method of permutation and combination to classify the drugs for Her-2 targeted therapy, and analyzed the most common drugs (mainly the drugs recommended by NCCN) through single comparison, single-double comparison and pairwise comparison, and analyzed the related neoadjuvant/ adjuvant chemotherapy, early / advanced breast cancer, first / second line clinical trials, so as to systematically summarize the previous clinical data on targeted therapy. RESULTS In single comparison, tratuzumab is still strong, while T-DM1 is developing. In single double comparison, T+P is strong and T-DM1+L will be promising in the short term, more combination therapy included ADC and targeted drugs are potential to be developed. Meanwhile, TKI and ADC for BCBM and more newly developed ADC are presence of new drug trials. What's more, the ADC drugs is developed targeted more. CONCLUSIONS We point out the research direction and potential breakthrough of targeted therapy in the future, hoping to provide the most direct help to the clinical practice.

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Impact of adjuvant trastuzumab on outcomes of HER2-positive breast cancer patients treated with HER2-targeted therapy in the metastatic setting.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.527 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 527-527

Author(s):

Rashmi Krishna Murthy ◽

Ankur Varma ◽

Priyankana Mishra ◽

Kenneth R. Hess ◽

Elliana J. Young ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Early Stage ◽

Menopausal Status ◽

Metastatic Breast ◽

Hazard Ratio ◽

Adjuvant Setting ◽

Her2 Breast Cancer ◽

Metastatic Setting ◽

Her 2

527 Background: Trastuzumab (T) was approved for the adjuvant treatment of women with early-stage, HER-2 overexpressing (HER2+) breast cancer in 2006. There are limited data outlining the outcomes of patients with HER2+ breast cancer who receive adjuvant T-based therapy and then receive T and/or lapatinib in the metastatic setting. Methods: We identified 540 patients with HER2+ breast cancer treated with T or lapatinib as part of their first-line treatment for metastatic disease from 01/1997 to 11/2011. HER-2 positivity was assessed by immunohistochemistry (score, 3+) or fluorescence in situ hybridization (HER2/CEP17 ratio ≥ 2). We excluded 17 patients from this analysis because they were either lost to follow-up or received less than 2 cycles of therapy at the institution. Statistical analyses were performed using the chi-square test to compare proportions between groups and the Cox proportional hazards regression analysis to compare survival times and estimate the corresponding hazard ratio with 95% confidence interval. Results: Of the 523 patients eligible for analysis, 76 patients had received T in the adjuvant setting and 447 had not. In the group who did not receive adjuvant T, 48% (213/447) of patients achieved a complete or partial response (CR/PR), whereas only 13% (14/76) achieved a CR/PR in the adjuvant T group (P<.0001). After adjustment for age, disease-free interval, post-menopausal status, stage at presentation, ER/PR status, and nuclear grade, the odds ratio was 0.27 (CI 0.13 - 0.56, p = 0.0004). Overall survival from first evidence of metastasis was significantly longer in the group who did not receive adjuvant T (39 months vs. 24 months, HR = 1.8, 95% CI 1.3-2.4). For OS, the adjusted hazard ratio was 1.5 (CI 1.04 - 2.1, p = 0.029). Age, DFI and stage were also significant predictors of OS. Conclusions: Patients with HER2+ metastatic breast cancer who were T naive, had a higher response rate (CR/PR) to front line HER2 targeted therapy and a longer OS compared to patients with metastatic HER2+ breast cancer who received T in the adjuvant setting. These findings highlight the importance of recognizing a pre-treated population and calls for further research in this area.

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Effect of neoadjuvant pertuzumab-containing regimens on pathologic complete response rates in stage II-III HER2-neu positive breast cancer: A retrospective, single institutional experience.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.580 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 580-580

Author(s):

Rashmi Krishna Murthy ◽

Takeo Fujii ◽

Kenneth R. Hess ◽

Akshara Singareeka Raghavendra ◽

Bora Lim ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Clinical Stage ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Complete Response ◽

Stage Ii ◽

Her2 Positive ◽

Her2 Breast Cancer ◽

Positive Breast Cancer

580 Background: Pertuzumab (P) in combination with trastuzumab (H) based chemotherapy is currently FDA- approved as a standard neoadjuvant treatment for patients with clinical stage II-III HER2-positive (HER2+) breast cancer (BC). The chemotherapy backbone of HER2-targeted therapy varies and may include taxane (T) and/or anthracycline (A), or carboplatin (C). The goal of this study was to retrospectively evaluate the pathologic complete response (pCR) rate for HP-containing regimens compared to H containing regimens for stage II-III HER2+ BC. Methods: We identified all patients (n = 1150) with stage II-III HER2+ BC who received neoadjuvant HER2-targeted therapy from 2005 to 2016 through an institutional database. All patients underwent primary breast and lymph node surgery. pCR was defined as ypT0/is, ypN0. Univariate/multivariate logistic regression and chi-squared test for comparing proportions was used for the statistical analysis. Results: pCR was significantly higher for the HP group (n = 200) compared to the H group (n = 950): 44% vs. 41%, odds ratio = 1.8 (95% CI = 1.3, 2.5; P = 0.0002). Even with adjustment for all clinically significant factors (age, stage, tumor grade, hormone receptor (HR) status, A or C exposure), the improvement was statistically significant (adjusted OR = 2.1 (95% CI = 1.5, 2.9; P < 0.0001). The pCR rate by stage and HR status for the HP group is 62% vs. 55% (stage II vs. III) and 71% vs. 51% (HR- vs. HR+). The effect of P was not modified by HR status (HR-, OR = 2.3; HR+, OR = 1.7, P = 0.39) or by A (A-yes, OR = 1.8; A-no, OR = 2.6) (P = 0.28 for interaction) or C (C-yes, OR 2.6; C-no, OR = 1.8) (P = 0.30 for interaction). P was significantly more likely to be given to patients without A (36% vs. 10%, P < 0.0001) and more likely to be given to patients with C (30% vs. 14%, P < 0.001). In both groups, significant predictors of pCR were found to be stage, HR status, and C exposure. Conclusions: Pertuzumab containing regimens yield higher pCR rates compared to non-Pertuzumab containing regimens in stage II- III HER-2 positive breast cancer. The effect of Pertuzumab is not modified by anthracycline or carboplatin use.

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Dual HER-2 blockade therapy increases the risk of developing cardiac toxicities in HER-2 positive breast cancer: an up-to-date comprehensive meta-analysis

10.21203/rs.2.24445/v1 ◽

2020 ◽

Author(s):

Wei-Xiang Qi ◽

Lu Cao ◽

Cheng Xu ◽

Shengguang Zhao ◽

Jiayi Chen

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Cancer Patients ◽

Fixed Effects ◽

Group Analysis ◽

Cochrane Library ◽

Close Monitoring ◽

Breast Cancer Patients ◽

Her 2 ◽

Positive Breast Cancer

Abstract Background To investigate the incidence and risk of cardiac toxicities between dual HER-2 blockade and anti-HER-2 monotherapy.Materials and Methods We searched PubMed, EMBASE and Cochrane library databases to identify relevant trials between January 1 1990 and October 31 2019. Statistical analyses were conducted to calculate the summary incidence, Petro odds radio (Peto ORs) and 95% confidence intervals (CIs) by using either random-effects or fixed-effects models.Results A total of 16,375 patients from 15 randomized controlled trials were included for analysis; the pooled incidence of LVEF decline and CHF in dual HER-2 blocked were 4.6% and 0.9%, which was higher than that in anti-HER-2 monotherapy (3.2% and 0.7%, respectively). Dual HER-2 blockade therapy in breast cancer patients significantly increased the risk of developing LVEF decline (OR:1.19, 95%CI: 1.02-1.40, p=0.031) and CHF (OR:1.45, 95%CI: 1.00-2.11, p=0.049) when compared to anti-HER2 monotherapy. Sub-group analysis showed that addition of dual HER-2 blockade to adjuvant treatment for breast cancer significantly increased the risk of developing LVEF decline (p=0.048) and CHF (p=0.005). In addition, dual HER-2 blockade in breast cancer patients significantly increased the risk of developing LVEF decline (p=0.004) when compared to lapatinib alone, but not for CHF (p=0.11, respectively).Conclusion Dual HER-2 targeted therapy in HER-2 positive breast cancer significantly increase the risk of developing LVEF and CHF when compared to anti-HER-2 alone, though the overall incidence of cardiac toxicities is very low. Physicians should be aware of this risk and provide close monitoring during the administration of dual HER-2 targeted therapy.

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