Abemaciclib-induced lung damage leading to discontinuation in brain metastases from breast cancer: A case report.

BACKGROUND: This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer. It presents a unique case of a woman with estrogen receptor-positive, HER2-negative breast cancer who developed brain metastasis. The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discontinuation due to drug-induced lung damage (DILD). CASE SUMMARY: In this comprehensive case summary, we present the clinical course of a woman in her 60s, who 11 years following primary breast cancer surgery, was diagnosed with multiple brain metastases. As a third-line systemic therapy, she underwent treatment with abemaciclib and letrozole. This treatment approach yielded a near-partial response in her metastatic brain lesions. However, abemaciclib administration ceased due to the emergence of DILD, as confirmed by a computed tomography scan. The DILD improved after 1 mo of cessation. Despite ongoing therapeutic efforts, the patient's condition progressively deteriorated, ultimately resulting in death due to progression of the brain metastases. CONCLUSION: This case underscores the challenge of managing adverse events in responsive brain metastasis patients, given the scarcity of therapeutic options.

Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subset of breast cancer that results from overexpression of HER2 protein. Pertuzumab-a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2-was recently approved for adjuvant therapy and neoadjuvant therapy of HER2-positive early breast cancer. As pertuzumab and trastuzumab bind to different domains of the extracellular dimerization domain of HER2, a combination therapy of pertuzumab and trastuzumab is beneficial for the treatment of metastatic cancer, advanced local cancer, or early cancer by dual HER2 blockage. Many clinical trials have been performed using pertuzumab for breast cancer patients; these include the CLEOPATRA trial for palliative therapy, the APHINITY trial for adjuvant therapy, and the NeoSphere and the TRYPHAENA trials for neoadjuvant therapy. These trials revealed pertuzumab to be a safe and effective drug regardless of the patient age and hormone receptor status. Notably, pertuzumab use was associated with severe cardiac toxicity in some cases; however, the risk of pertuzumab-induced cardiac dysfunction was low. The most common adverse effect associated with pertuzumab-use was diarrhea, but most cases were not severe. Several different chemotherapeutic agents have been investigated to determine optimal chemotherapeutic combinations for dual HER2 blockage. Some exploratory analyses indicate that pertuzumab treatment offered little benefit to patients with node-negative and small primary tumors; pertuzumab treatment was also found not be cost-effective. Further research will reveal the appropriate usage of pertuzumab for treating a subset of eligible patients.

Pathological complete response rate in hormone receptor-negative breast cancer treated with neoadjuvant FEC, followed by weekly paclitaxel administration: A retrospective study and review of the literature.

While tumor size, the presence of inflammatory carcinoma and lymph node involvement are the main prognostic factors of women with locally advanced breast cancer, the prognostic value of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) status has not been fully clarified. The present study examined the therapeutic efficacy of a neoadjuvant fluorouracil, epirubicin and cyclophosphamide regimen (FEC), followed by weekly paclitaxel and/or trastuzumab administration, in the treatment of hormone receptor-negative breast cancer patients. Between April 2012 and February 2014, 14 patients with hormone receptor-negative local breast cancer (triple-negative type, 9 patients; HER2 type, 5 patients) were included in the study. In all cases, the histological type of the primary cancer was invasive ductal carcinoma. Among the 14 women who received the regimen, 5 presented with stage I cancer (35.7%), 3 with stage IIA (21.4%), 3 with stage IIB (21.4%), 1 with stage IIIB (7.1%) and 2 with stage IIIC (14.3%), according to the American Joint Committee on Cancer staging system. With regard to the tumor-node-metastasis classification, 5 patients were T1N0M0 (35.7%), 3 were T2N0M0 (21.4%), 3 were T2N1M0 (21.4%), 2 were T3N3M0 (14.3%) and 1 was T4N1M0 (7.1%). The pathological response was evaluated using resected tissue following neoadjuvant chemotherapy, according to the criteria established by the Japanese Breast Cancer Society. Patients were classified into pathological responders (grades 2 and 3, 71.4% of all patients) and non-responders (grade 1, 28.6% of all patients). A pathological complete response (pCR) was achieved in 50.0% of all cases (7/14); 44.4% of triple-negative-type cases (4/9) and 60.0% of HER2-type cases (3/5). Hematological and non-hematological toxicity was reversible and manageable. No patients withdrew from treatment, and favorable compliance was achieved. The present study demonstrated that neoadjuvant FEC followed by weekly administration of paclitaxel and/or trastuzumab induces a high pathological response and a high pCR rate in patients with hormone receptor-negative breast cancer. Due to the high clinical benefit rate and acceptable safety profile, this regimen should be considered an acceptable neoadjuvant treatment option for hormone receptor-negative breast cancer.

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.

Pathological response rate in hormone-positive breast cancer patients treated with neoadjuvant FEC and triweekly docetaxel: a case series.

We recently reported that neoadjuvant 5-FU, epirubicin, and cyclophosphamide (FEC) followed by weekly paclitaxel and/or trastuzumab induced a high pathological complete response (pCR) rate in hormone-negative patients. The present study examined the therapeutic efficacy of neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab in the treatment of hormone-positive patients. Between February 2012 and December 2013, 16 hormone-positive patients with local breast cancer (luminal A type: six patients; luminal B type: two patients; luminal HER2 type: eight patients) were included in the study. The histological type of the primary cancer was invasive ductal carcinoma in all patients. The cancer stages in the 16 women who received this regimen were stage I in five (31.3%), IIA in four (25.0%), IIB in five (31.3%), IIIB in one (6.3%), and IIIC in one (6.3%). Regarding clinical TNM classification, five patients were T1N0M0, one was T1N1M0, three were T2N0M0, five were T2N1M0, one was T3N2M0, and one was T4N0M0. The pCR was evaluated using resected tissue after neoadjuvant chemotherapy according to the evaluation criteria of the Japanese Breast Cancer Society. Patients were classified into pathologic responders (grade 2: 50.0% of all patients: 2/6 of luminal A type; 6/8 of Luminal HER2 type) and nonresponders (grades 0 and 1: 50.0% of all patients: 4/6 of luminal A type; 2/2 of luminal B type; 2/8 of luminal HER2 type) according to the grade of the tumor. The pCR rate was 0%. Hematologic and nonhematologic toxicity was reversible and manageable. This study demonstrated that neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab did induce a high pathologic response in luminal HER2 type, but not in luminal A and B types, and did not induce a high pCR rate in the hormone-positive patients.

[A case of Paclitaxel-induced peripheral neuropathy successfully treated with duloxetine].

Here, we report about a 60-year-old woman with metastatic breast cancer who was successfully treated for paclitaxelinduced peripheral neuropathy with duloxetine. She was administered trastuzumab plus paclitaxel(PTX)combination therapy that was ultimately discontinued because of grade 3 peripheral neuropathy detected on day 15, according to the CTCAE (v4.0). She was administered duloxetine on day 90 after the end of the previous therapy because of the peripheral neuropathy. Thereafter, the peripheral neuropathy decreased to grade 1, which enabled PTX administration on her request. Further trials are required to confirm the efficacy of duloxetine.

[Effect of dexamethasone on vascular pain caused by the administration of fosaprepitant dimeglumine and epirubicin hydrochloride in patients with primary breast cancer].

Epirubicin hydrochloride injection is indicated as a therapy for patients with primary breast cancer. This drug has been reclassified as a drug with high emetic potential according to the American Society of Clinical Oncology Guidelines for Antiemetics in Oncology. Therefore, patients who receive this agent should also receive fosaprepitant dimeglumine, an anti-emetic agent. However, it has been reported that fosaprepitant induces vascular pain when used in anthracycline-based regimens administered via the peripheral veins. In order to relieve the fosaprepitant and epirubicin-induced vascular pain associated with vasculitis, dexamethasone was administered at the onset of vascular pain. There is a possibility that the fosaprepitant and epirubicin-induced pain may improve owing to the administration of dexamethasone; however, further trials are required to confirm the effect of this method.

Synthetic curcumin analog UBS109 inhibits the growth of head and neck squamous cell carcinoma xenografts.

The natural compound curcumin has been investigated as an anticancer agent in many cellular systems, in animal models and in the clinic. The overriding negative characteristics of curcumin are its low solubility, weak potency and poor bioavailability. We have examined the efficacy and mechanism of action of a synthetic curcumin analog, UBS109, in head and neck squamous cell carcinoma. By nephelometry, this analog exhibits considerably greater solubility than curcumin. Pharmacokinetic studies of a single oral dose of UBS109 in mice revealed that peak plasma concentrations were reached at 0.5 hours post-dose (Tmax) with average plasma concentrations (Cmax) of 131 and 248 ng/mL for oral doses of 50 and 150 mg/kg, respectively. The terminal elimination half-lives (T½) for these doses averaged 3.7 and 4.5 hours, respectively. In both in vitro and in vivo studies, we found that UBS109 decreased the levels of phosphorylated IKKß and phosphorylated p65 and, unexpectedly, increased the levels of phosphorylated IκBα by Western blot analysis. These observations may suggest that UBS109 suppresses tumor growth through, in part, inhibition of NF-κB p65 phosphorylation by PKAc and not through IκBα. Finally, we demonstrate that UBS109 is efficacious in retarding the growth of Tu212 (head and neck) squamous cell carcinoma (SCC) xenograft tumors in mice and may be useful for treating head and neck SCC tumors.

Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts.

Objectives are to examine the efficacy, pharmacokinetics, and toxicology of a synthetic curcumin analog EF31 in head and neck squamous cell carcinoma. The synthesis of EF31 was described for the first time. Solubility of EF24 and EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5-6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg kg(-1), i.p. inhibited tumor growth almost completely. Solubilities of EF24 and EF31 are <10 and 13 µg mL(-1) or <32 and 47 µM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, they revealed a linear increase of C(max). EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analog EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-κB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis.