The safety and efficacy of<unk> -containing combination therapies (with chemotherapy, hormone blockers, or lapatinib) for the treatment of metastatic breast cancer. The overall hazard ratios for overall survival and progression free survival were 0.82 and 0.61, respectively. It was difficult to accurately ascertain the true impact of<unk>  on survival, as in three of the seven trials, over half of the patients in the control arm were allowed to cross-over and receive<unk>  after their cancer began to progress. Thus, this analysis likely underestimates the true survival benefit associated with<unk>  treatment in this population. In these trials,<unk>  also increased the risk of heart problems, including heart failure and left ventricular ejection fraction decline. In early-stage HER2-positive breast cancer,<unk> -containing regimens improved overall survival (HR = 0.66) and disease-free survival (HR = 0.60). Increased risk of heart failure (RR = 5.11) and decline in left ventricular ejection fraction (RR = 1.83) were seen in these trials as well. Two trials involving shorter term treatment with<unk>  did not differ in efficacy from longer trials, but produced less cardiac toxicity. The original studies of<unk>  showed that it improved overall survival in late-stage (metastatic) HER2-positive breast cancer from 20.3 to 25.1 months. In early-stage HER2-positive breast cancer, it reduces the risk of cancer returning after surgery. The absolute reduction in the risk of cancer returning within 3 years was 9.5%, and the absolute reduction in the risk of death within 3 years was reduced by 3%. However, it increases serious heart problems by an absolute risk of 2.1%, though the problems may resolve if treatment is stopped.<unk>  has had a "major impact in the treatment of HER2-positive metastatic breast cancer." The combination of<unk>  with chemotherapy has been shown to increase both survival and response rate, in comparison to<unk>  alone. It is possible to determine the "erbB2 status" of a tumor, which can be used to predict efficacy of treatment with<unk> . If it is determined that a tumor is overexpressing the erbB2 oncogene and the patient has no significant pre-existing heart disease, then a patient is eligible for treatment with<unk> . It is surprising that although<unk>  has great affinity for HER2 and high doses can be administered (because of its low toxicity), 70% of HER2+ patients do not respond to treatment. In fact resistance to the treatment develops rapidly, in virtually all patients. A mechanism of resistance involves failure to downregulate p27 (Kip1) as well as suppressing p27 translocation to the nucleus in breast cancer, enabling cdk2 to induce cell proliferation. In May 2021, the FDA approved pembrolizumab in combination with<unk> , fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of people with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. Duration of treatment The optimal duration of add-on<unk>  treatment after surgery for early breast cancer is unknown. One year of treatment is generally accepted based on clinical trial evidence that demonstrated the superiority of one-year treatment over none. However, a small Finnish trial also showed similar improvement with nine weeks of treatment over no therapy. Because of the lack of direct head-to-head comparison in clinical trials, it is unknown whether a shorter duration of treatment may be just as effective (with fewer side effects) than the accepted practice of treatment for one year. Debate about treatment duration has become a relevant issue for many public health policy makers because administering<unk>  for a year is very expensive. Consequently, some countries with a taxpayer-funded public health system, such as New Zealand, chose to fund limited adjuvant therapy. However, subsequently New Zealand has revised its policy and now funds<unk>  treatment for up to 12 months.
Trastuzumab
Docetaxel
Tamoxifen
Paclitaxel
Ribociclib
Cetuximab
Palbociclib
N-Desmethyltamoxifen