4.2. Extended adjuvant endocrine therapy beyond 5 years

Adjuvant endocrine therapy for 5 years is the standard adjuvant treatment for ER+ breast cancer while the benefits of extended adjuvant endocrine therapy (EAET) beyond 5 years are still controversial. In a recent meta-analysis, 5 years of adjuvant endocrine therapy only was compared with EAET [52]. Eleven controlled trials including 29,000 women were analyzed. There was no advantage of EAET in OS from all causes mortality (P = 0.67). On the other hand, compared with standard therapy, the pooled effects showed that EAET was associated with improvement in breast cancer-specific survival (OR = 0.87; P = 0.004), DFS (OR = 0.87; P = 0.002), disease recurrence (OR = 0.76; P = 0.001), and contralateral breast recurrence (OR = 0.74; P = 0.008). Improvement in DFS or disease recurrence was not shown in studies that compared 5 years of tamoxifen versus tamoxifen beyond 5 years. Subgroup analysis showed that EAET conferred more benefit for patients with positive lymph nodes. Rates of positive lymph nodes, the study size, and the median duration of follow-up were identified as variables that explained most of the demonstrated data heterogeneity. EAET should be considered as a preferred strategy for high-risk hormone-positive early breast cancer patients with positive lymph nodes; however, the benefit on OS could not be demonstrated.

Extended adjuvant endocrine therapy results in increased toxicity based on the type of extended endocrine agents. Risk of bone fractures is reported to be higher with AI, whereas the risk of endometrial cancer and venous thromboembolism are more frequently than with TAM. No difference was shown between AI (mono- or sequenced therapy) and TAM for cardiovascular events, whereas sequenced therapy compared with AI had lower risk of cardiovascular events (moderate level of evidence).

5. Adjuvant bisphosphonates

scope of the guideline.

6. Promising targeted agents

I confirm there are no conflicts of interest.

Address all correspondence to: fatmasen840@gmail.com

Avrasya Hospital, Medical Oncology Unit, Zeytinburnu, Istanbul, Turkey

early-stage HR+ breast cancer.

Conflict of interest

Author details

Fatma Sen

Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations by a systematic review of the literature [55]. The women with natural menopause or the women who were postmenopausal induced by ovarian suppression or ablation were included. Adjuvant bisphosphonates were reported to reduce bone recurrence and improve survival in postmenopausal women with early stage breast cancer. Absolute benefit was found to be greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. The data are extremely limited for bisphosphonates other than zoledronic acid or clodronate due to most studies performed with these two bisphosphonates. ASCO clinical guidelines recommends that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1600 mg/d orally) be considered as an adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. However, further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. While adjuvant denosumab reduces fractures and it looks promising in adjuvant setting, long-term survival data are still insufficient to make any recommendation. The use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the

Adjuvant Systemic Treatment in Hormone Receptor Positive, HER2 Negative Breast Cancer

http://dx.doi.org/10.5772/intechopen.76578

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Ongoing studies are evaluating the role of additional targeted therapies, such as CDK4/6 inhibitors including ribociclib, palbociclib, to further improve outcome for patients with
