Abstract
Systemic therapies for operable breast cancer patients have improved outcomes and have thus become standard treatments. Recently, new molecular target drugs and regimens are being developed ...based on the predicted sensitivity for specific breast cancer histological types. Systemic therapy is selected according to recurrence risk, with the treatment for low-risk patients being de-escalated, while high-risk patients receive aggressive systemic treatment with an adequate dose and duration. Neoadjuvant systemic therapy has a different aim. The efficacy of systemic therapies, based on the sensitivities to drugs, is supported by improvements in the rate of breast-conserving therapy. The response to neoadjuvant systemic therapy is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers unique to individual patients allow appropriate targeted therapy, which can achieve optimal efficacy.
Endocrine therapy is the mainstay of treatment for patients with estrogen receptor positive (ER+)/HER2-negative (HER2−) metastatic breast cancer (MBC). Many clinicians consider the sequential ...endocrine therapy is gold standard strategy because of better outcome and the maintenance of a better quality of life (QOL) for MBC patients. However, clinical practice shall be changed according to development of CDK4/6 inhibitor in current. CDK4/6 is key kinase which promote the cell cycle, and especially the expression of cyclin D1 and the activation of CDK4/6 to drive breast cancer proliferation. Currently positive data of several clinical trials using three CDK4/6 inhibitors (palbocilcib, ribociclib, abemaciclib) were published and primary endpoint were met in all phase III studies. Therefore, practice change of endocrine therapy has been achieved in ER positive MBC. This review will present clinical trial data, including both the efficacy and safety of CDK4/6 inhibitors for MBC, and describe the designs of the mainly ongoing clinical trials examining CDK4/6 inhibitors for the treatment of MBC and EBC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PIK3CA
mutations occur in approximately 40% of patients with hormone receptor–positive breast cancer. A PI3K inhibitor, alpelisib, combined with fulvestrant led to a median progression-free survival ...of 11 months, as compared with 5.7 months with placebo plus fulvestrant. Hyperglycemia, rash, and diarrhea were more common with alpelisib.
In women with hormone-receptor–positive metastatic breast cancer that had progressed after endocrine therapy, palbociclib plus fulvestrant was associated with progression-free survival of more than 9 ...months, as compared with less than 4 months with fulvestrant alone.
Approximately 80% of breast cancers express estrogen receptors, progesterone receptors, or both. Endocrine therapies are the mainstay of treatment for these hormone-receptor–positive cancers, substantially reducing the relapse rate after presentation with early-stage cancer.
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Despite advances in endocrine therapy, many women have a relapse during or after completing adjuvant therapy. The care of these women remains a considerable clinical challenge. Single-agent treatment with an aromatase inhibitor or tamoxifen has shown limited clinical benefit.
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The selective estrogen-receptor degrader fulvestrant has modest activity in this population of patients,
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and the development of effective therapies that can reverse resistance to endocrine therapy . . .
Ductal carcinoma in situ (DCIS) has a good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. In ductal carcinoma in situ without ...micrometastasis, surgery and postoperative adjuvant therapy significantly improve local control, however it has been reported that the selection of the surgical procedure and adjuvant therapy does not influence breast cancer death. On the other hand, owing to widespread mammography screening, the frequency of early breast cancer detection has increased. In early breast cancer, increased incidence of DCIS is remarkable. However, there is not enough reduction of advanced cancer to match it. Problems with overdiagnosis are now being discussed all over the world. It has been reported that surgery for low-grade ductal carcinoma in situ does not contribute to breast cancer-specific survival. However, it is currently impossible to reliably identify a population that does not progress to invasive cancer even without treatment. Recently, a non-surgery clinical trial for low-risk ductal carcinoma in situ was started. There is a possibility of achieving individualized treatment for ductal carcinoma in situ with less treatment intervention, without compromising the good prognosis obtained with the current treatment approach. This review presents an overview of the current treatment approaches, problems with overdiagnosis and potential future management strategies for ductal carcinoma in situ of the breast.
At the MONARCH 3 interim analysis, abemaciclib plus a nonsteroidal aromatase inhibitor (AI) significantly improved progression-free survival (PFS) and objective response rate (ORR) with a tolerable ...safety profile as initial treatment for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). MONARCH 3 is a randomized, phase III, double-blind study of abemaciclib/placebo (150 mg twice daily, continuous) plus nonsteroidal AI (1 mg anastrozole or 2.5 mg letrozole, daily). A total of 493 postmenopausal women with HR+, HER2- ABC with no prior systemic therapy in this setting were enrolled. The primary endpoint was investigator-assessed PFS (final analysis after 240 events); other endpoints included response and safety evaluations. Here we analyze the final PFS data and update secondary endpoints. The abemaciclib arm had a significantly longer median PFS than the placebo arm (28.18 versus 14.76 months; hazard ratio 95% confidence interval, 0.540 0.418-0.698;
= .000002). The ORR was 61.0% in the abemaciclib arm versus 45.5% in the placebo arm (measurable disease,
= .003). The median duration of response was longer in the abemaciclib arm (27.39 months) compared to the placebo arm (17.46 months). The safety profile was consistent with previous reports. The most frequent grade ≥ 3 adverse events in the abemaciclib versus placebo arms were neutropenia (23.9% versus 1.2%), diarrhea (9.5% versus 1.2%), and leukopenia (8.6% versus 0.6%). Abemaciclib plus a nonsteroidal AI was an effective initial treatment with an acceptable safety profile for HR+, HER2- ABC.
In this single-group, phase 2 study, the use of trastuzumab deruxtecan resulted in a response in 60% of women with HER2-positive advanced breast cancer who had received a median of six previous lines ...of therapy. The drug was associated with myelosuppression and gastrointestinal toxicity; interstitial lung disease was reported in 13.6% of the patients.
Addition of the anti–PD-L1 antibody atezolizumab to nab-paclitaxel as first-line therapy for patients with advanced or metastatic triple-negative breast cancer significantly prolonged ...progression-free survival, particularly among those with PD-L1–positive tumors.
Among patients with triple-negative breast cancer and high expression of PD-L1, pembrolizumab plus chemotherapy resulted in longer overall survival than chemotherapy alone.
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