HER2-positive Recurrent Breast Cancer Research Articles

Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer.

There are limited studies reported that describe the efficacy of eribulin and trastuzumab in the treatment of recurrent breast cancer. The present study examined the therapeutic efficacy of eribulin and trastuzumab in the treatment of recurrent breast cancer. Between October 2011 and August 2013, 5 recurrent breast cancer patients who were treated with eribulin and trastuzumab were included in the study. The cancer stages in the 5 women who received this regimen were stage IIIB in 1 (20%) and stage IV in 4 (80%). The sites of recurrence were the lung in 3 patients, liver in 2, bone in 1, brain in 1, supraclavicular lymph nodes in 1, infraclavicular lymph nodes in 1 and mediastinal lymph nodes in 1. The median number of prior treatment regimens was 5 (range, 5-11). Complete response was achieved in 0 patients, 1 achieved partial response, 3 had stable disease, and 1 had progressive disease. The overall response rate was 20%, and the clinical benefit rate was 80%. Patients also reported grade 3/4 neutropenia (80.0%). However, hematological toxicity was reversible and manageable. The most common grade 3/4 nonhematological toxicities were fatigue (20.0%), peripheral neuropathy (20.0%) and appetite loss (20.0%). No patients withdrew from treatment, and favorable compliance was achieved in the study. The results indicated that eribulin and trastuzumab have the potential to be one of the drugs for treatment of recurrent breast cancer.

HER2-positive recurrent breast cancer and metastases of breast cancer, including life-threatening metastases to the brain and dura mater: a case effectively treated with lapatinib plus capecitabine before whole brain radiotherapy

Lapatinib is a new small molecule tyrosine kinase inhibitor. It targets both ErbB1 and ErbB2 (HER2) receptors and directly and reversibly acts on them to inhibit signaling. Since lapatinib has a low molecular weight, it can cross the blood–brain barrier. Thus, there is much interest in its potential effectiveness against brain metastases. Our patient was a 57-year-old postmenopausal woman with a non-contributory medical history. In September 2006, she underwent a partial mastectomy and axillary dissection for right breast cancer. Pathological diagnosis was solid-tubular carcinoma, n+ (6/23), nuclear grade 3, ly1, v0, ER+, PgR−, and HER2 3+ (pT1cN2aM0-stageIIIA). Adjuvant chemotherapy consisted of 6 cycles of epirubicin and cyclophosphamide (EC) and subsequent oral anastrozole. In May 2009, the patient developed choroidal, lung, liver, bone, and lymph node metastases. She underwent radiation therapy (choroids 40 Gy and cervical vertebrae 40 Gy), and the oral drug was changed to high-dose toremifene. In July 2009, the patient developed headache, vomiting, and seizures. MRI revealed multiple brain metastases and dura mater metastases. Administration of glycerol and steroid was begun. In addition, administration of lapatinib (1,250 mg/body, daily) plus capecitabine (2,000 mg/m2, day 1–14, every 3 weeks) was begun for treatment of brain and systemic metastatic lesions. Neurological symptoms improved on day 14. In January 2010, examinations revealed partial response of all metastatic lesions, including brain metastases. The patients continued the same treatment but exhibited progressive disease in March 2010. Thus, the treatment was discontinued as per the patient’s request. In May 2010, the patient developed generalized seizures again and underwent whole brain radiotherapy (30 Gy). However, the patient’s general condition gradually deteriorated and the patient died in June 2010.

Trastuzumab monotherapy versus combination therapy for treating recurrent breast cancer: time to progression and survival

HER2 expression is an important prognostic and predictive factor of treatment efficacy in breast cancer. Trastuzumab, in particular, is a key drug in the treatment of HER2-positive recurrent breast cancer. However, the difference in treatment efficacy between trastuzumab monotherapy and combination therapy with chemotherapy is unclear. In order to elucidate this point, both treatments were compared in terms of efficacy by metastatic site, time to progression (TTP), and survival. The subjects were 1,471 breast cancer patients who had been evaluated for HER2 expression between 1998 and March 2006; 74 of these had recurrent breast cancer that had been treated with trastuzumab. Of these 74 patients, 39 received trastuzumab alone and 45 trastuzumab in combination with chemotherapy. The items of investigation were clinical effect, TTP, survival, biological markers such as ER/PgR, proliferation (Ki67) or p53 overexpression, nuclear grade, performance status (PS), lymph node metastasis, and tumor size. The HER2-positive rate was 23.3%, and the degree of malignancy in these HER2-positive patients was high; postoperative disease-free survival (DFS) was low. However, this tendency was clear in patients with hormone-responsive breast cancer. In patients with hormone-non-responsive breast cancer, HER2 negativity had a significantly higher Ki67 value, and there was no difference in DFS between patients with HER2-positive and -negative tumors. Among the 74 patients with recurrent breast cancer, the response rate to trastuzumab was 64.9%; however, among patients who received the combination treatment, the response rate was 86%. In patients with liver metastasis, the effect of trastuzumab alone was low, but that of the combination treatment was significantly high. TTP was 5.7 months and 15.9 months with trastuzumab alone and the combination therapy, respectively. Furthermore, a significant difference was seen in post-treatment survival; however, there was no significant difference in survival after a recurrence. In the multivariate analysis on factors for TTP, PS, clinical effect, and combination treatment were significant. However, good PS and early treatment were the significant factors in post-treatment survival. The effect of trastuzumab in patients with recurrent breast cancer who received the combination treatment was significantly high and TTP was long. However, this was not a significant factor in terms of overall survival. In particular, a good PS and early treatment were important in post-treatment survival.

Three-weekly (q3w) trastuzumab (H) plus chemotherapy in HER2-positive recurrent breast cancer (RBC)

842 Background: The safety profile of weekly H is well known. However, recent studies have shown that H 6mg/kg q3w is as well tolerated and maintains therapeutic H levels over 21 days. Based on these data, we have investigated H q3w plus docetaxel (T), vinorelbine (N) or capecitabine (X). Methods: 31 patients (pts) with HER2-positive (23 IHC 3+, 8 IHC2+/FISH-positive) disease were enrolled. 20 pts were treated first line (prior adjuvant chemotherapy allowed). 11 patients had received prior therapy for RBC (1–3 regimens). Drug doses: H–8mg/kg loading, 6mg/kg q3w, day (d)1; T–100mg/m2, d1; N–25mg/m2, d1/8; X–2500 mg/m2, d1–14. Treatment was discontinued or cytotoxic changed upon disease progression. Results: H was combined with T, N or X in 11, 11 and 12 patients respectively. A total of 293 courses have been given (range 3–30, median 9.45). In 2 pts, N replaced X and in one pt X replaced N upon progression. In one pt, T was given after X and N. 2 pts received H/T plus carboplatin and one received H/N plus gemcitabine. In 2 IHC2+/FISH-positive pts, treatment was discontinued after FISH reassessment (these pts were included in the toxicity evaluation). Overall, the q3w H-containing regimens were well tolerated. The majority of toxicities observed were typical of the cytotoxics administered. Five pts displayed H infusion-related reactions. One H/X pt with previous anthracycline exposure displayed a grade 2 decrease in LVEF, associated with an intraventricular clot and persistant hypokalaemia. H, but not X, was discontinued and LVEF normalised 6 months later. One H/T pt with known lymhangitic pulmonary disease had transient post-infusion dyspnea. Although, given the heterogeneity of the study, efficacy of the q3w schedule cannot be evaluated, 18 clinical responses (3 CR, 15 PR), 8 cases of stable disease and 5 of progressive disease have been documented after ≥3 courses. Median time to progression, duration of response and survival have not yet been reached. Conclusion: In this small, heterogeneous group of pts, q3w H plus chemotherapy seems to be as well tolerated and active as weekly H. No significant financial relationships to disclose.

Three-weekly (q3w) trastuzumab (H) plus chemotherapy in HER2-positive recurrent breast cancer (RBC)

842 Background: The safety profile of weekly H is well known. However, recent studies have shown that H 6mg/kg q3w is as well tolerated and maintains therapeutic H levels over 21 days. Based on these data, we have investigated H q3w plus docetaxel (T), vinorelbine (N) or capecitabine (X). Methods: 31 patients (pts) with HER2-positive (23 IHC 3+, 8 IHC2+/FISH-positive) disease were enrolled. 20 pts were treated first line (prior adjuvant chemotherapy allowed). 11 patients had received prior therapy for RBC (1–3 regimens). Drug doses: H–8mg/kg loading, 6mg/kg q3w, day (d)1; T–100mg/m2, d1; N–25mg/m2, d1/8; X–2500 mg/m2, d1–14. Treatment was discontinued or cytotoxic changed upon disease progression. Results: H was combined with T, N or X in 11, 11 and 12 patients respectively. A total of 293 courses have been given (range 3–30, median 9.45). In 2 pts, N replaced X and in one pt X replaced N upon progression. In one pt, T was given after X and N. 2 pts received H/T plus carboplatin and one received H/N plus gemcitabine. In 2 IHC2+/FISH-positive pts, treatment was discontinued after FISH reassessment (these pts were included in the toxicity evaluation). Overall, the q3w H-containing regimens were well tolerated. The majority of toxicities observed were typical of the cytotoxics administered. Five pts displayed H infusion-related reactions. One H/X pt with previous anthracycline exposure displayed a grade 2 decrease in LVEF, associated with an intraventricular clot and persistant hypokalaemia. H, but not X, was discontinued and LVEF normalised 6 months later. One H/T pt with known lymhangitic pulmonary disease had transient post-infusion dyspnea. Although, given the heterogeneity of the study, efficacy of the q3w schedule cannot be evaluated, 18 clinical responses (3 CR, 15 PR), 8 cases of stable disease and 5 of progressive disease have been documented after ≥3 courses. Median time to progression, duration of response and survival have not yet been reached. Conclusion: In this small, heterogeneous group of pts, q3w H plus chemotherapy seems to be as well tolerated and active as weekly H. No significant financial relationships to disclose.