Biomedical Engineering Reference
In-Depth Information
5.4.1
Adjuvant Endocrine Therapy
After local and regional treatment, some patients eventually develop
local recurrence and/or distant metastasis. Adjuvant systemic
endocrine and chemotherapy are administered in order to achieve
treatment benefit in terms of increasing disease-free survival (DFS)
and/or overall survival (OS). The benefit from tamoxifen treatment
has been established since the meta-analysis conducted by the
EBCTCG through an international collaborative effort.2,27
2,27
In addition,
clinical evidence has demonstrated that chemotherapy is less
effective in some patients with HR+ and HER2-negative early breast
cancer.
Low-risk patients identified by the recently developed
Oncotype DX and MammaPrint assays can get cured with endocrine
therapy alone after locoregional therapy.
37,38
39,40
5.4.1.1 Premenopausal patients
Based on the existing evidence, tamoxifen 20 mg daily for 5 years
is recommended as adjuvant endocrine therapy for premenopausal
women with hormone receptor-positive invasive breast cancer by
major practice guidelines. The National Comprehensive Cancer
Network (NCCN) recommends that tamoxifen can be used alone if
tumors are small (≤0.5 cm) or have micro-invasion with minimal
lymph node involvement (≤ 2 mm in axillary node metastasis).
For patients with node-positive disease, tamoxifen is given after
chemotherapy and radiation therapy. If tumors are >0.5 cm but with
minimal lymph node involvement, tamoxifen is indicated regardless
of whether chemotherapy is recommended (
http://www.nccn.
org/professionals/physician_gls/f_guidelines.asp).
Tamoxifen is
well tolerated in general. The major known side effects include hot
flashes, thromboembolic event and endometrial cancer (Table 5.1).
Tamoxifen is teratogenic and reduces bone density in premenopausal
women.
41
For premenopausal patients taking tamoxifen, pregnancy
should be avoided. Bisphosphonates may be considered to prevent
bone loss. Because cytochrome P450 2D6 (CYP2D6) is required for
conversion of tamoxifen to its active metabolite, endoxifen, patients
with low levels of CYP2D6 activity may have reduced production
of endoxifen. CYP2D6 activity depends on the genetic variability of
patients and co-administration of other drugs that inhibit CYP2D6.
Although single nucleotide polymorphisms (SNPs) of CYP2D6 affect
the effectiveness of tamoxifen endocrine therapy by retrospective
