”The following 10 points are new to endocrine therapy in the Consensus and are concepts that clinicians must master. It is easy to see that many of these points have been applied in our clinical practice, so there is no doubt that breast cancer treatment in China is already on par with the world level, all we lack is clinical trials and basic research on new drugs, but with the gradual promotion of the latest research concepts in oncology in the future, we have reason to expect to finally beat cancer.”
1. The mechanism of hormone deprivation therapy is to cause apoptosis, and this effect is modulated by increased calcium aggregation. Apoptosis increases the expression of the G protein binding receptor (GPR30), which in turn is induced by its antagonist G1. Anti-angiogenic agents increase the effect of tamoxifen (TAM), high levels of cellular glutathione expression resist estrogenic effects, and application of the glutathione inhibitor BSO depleting glutathione will re-sensitize cells to estrogen treatment.
2, Crosstalk of ER and HER2
Studies have shown that crosstalk between the ER and HER2 pathways can lead to mutual effects of the two on each other’s efficacy, a result derived from studies of anti-ER therapy and epidermal growth factor receptor (EGFR) family therapy. Examples include the combination of gefitinib and TAM or anastrozole, and the combination of lapatinib and letrozole. More studies exploring the combination of HER2 and ER therapy are ongoing.
3. CYP2D6 enzymes
Another important study is related to cytochrome P450 2D6 (CYP2D6) abnormalities. We know that CYP2D6 is an important enzyme in the human liver, and TAM enters the body and becomes the active TAM metabolite Endoxifen under the action of CYP2D6 enzyme. Antidepressants can reduce the activity of this enzyme. Therefore, patients who are taking antidepressants are less effective when they receive TAM treatment at the same time. This suggests that increasing the dose of TAM may overcome the metabolism from TAM to Endoxifen in this group of patients. Nevertheless, most experts believe that CYP2D6 is not a routine test when patients are treated with TAM.
4. Genetic analysis and immunohistochemistry
Multi-gene analysis has been widely used to add useful prognostic information to classical pathology tests and in some cases to classify patients into different subgroups to determine whether they can benefit from adjuvant radiotherapy or chemotherapy. Studies have shown that the information obtained from genetic analysis led to a change in treatment decisions in 30% of patients, mainly avoiding chemotherapy. For hormone receptor-negative individuals, there is no information available. Studies of various gene expression profiles compared with the usual pathological examination have shown a new role for gene expression profiles in the use of hormone receptors, the EGFR family and proliferative factors, whereas previously these markers may have been used only for the selection of specific treatments and appear to be relevant only for proliferative factors in terms of prognostic information.
5. Endocrine therapy in premenopausal patients
TAM or TAM combined with ovarian function suppression for 5 years are both acceptable standard treatment regimens for endocrine responsive premenopausal women. Experts believe that ovarian function suppression alone or ovariectomy debulking should only be used in very specific cases. Aromatase inhibitors (AI) alone are contraindicated in premenopausal women. In patients with contraindications to TAM, AI may be used concomitantly with ovarian function inhibition. In such cases, it is important to confirm that ovarian function has been suppressed to postmenopausal levels.
6. Endocrine therapy in postmenopausal patients
Most experts believe that AI will be the standard adjuvant endocrine therapy for women with hormone receptor-positive postmenopausal breast cancer. The optimal interval of treatment is 2 to 5 years. There is still some disagreement among experts about the most appropriate interval for AI, and there is no safety information beyond 5 years.
7. AI and TAM
For some very low-risk patients, there is little difference between TAM and AI comparisons during the first 5 years of endocrine therapy. For such patients, it is best to consider patient tolerability in order to achieve maximum efficacy, minimal side effects, and minimal impact on health status and quality of life. And the initial use of AI is better for high-risk patients.
8. ER testing
Experts recommend that any detectable ER staining can be defined as ER positive and all tumors that respond to endocrine therapy should receive adjuvant endocrine therapy. If the ER is negative in PgR positive patients, they should further receive immunohistochemical confirmation.
9.Responsiveness to endocrine therapy
Endocrine therapy responsiveness has been simply defined as the presence of ER staining in the tumor. Most experts believe that the description of percentages in the pathology report is better than the score alone. Hormone receptor staining shows that if ≥50% of tumor cells are stained, it indicates an endocrine hyperresponsive tumor.
10. Correlation of receptor expression with chemotherapy
Low expression levels of ER and PgR are indications for chemotherapy, while high levels of ER and PgR expression are indications for endocrine therapy alone.