Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide, accounting for 25% of total cancer cases (Globocan, 2012) It ranks as the most prevalent cancer among women in the Middle East and Northern Africa (Ferlay et al., 2015). In Egypt, breast cancer is the most common type of cancer among females (Ibrahim et al., 2014).
Survival of breast cancer patients depends on the disease stage. Most of the patients with localized disease experience long-term disease-free survival. Meanwhile, those who develop metastasis have a 5-year relative survival of only 24% (Siegel et al, 2015). Hormonal receptor positive (HR +ve) represent the most common subset (almost 70%) in both early and advanced disease (Clarke et al., 2012).
It is crucial to determine the menopausal status before initiation of treatment. For HR +ve / Her 2-negative metastatic breast cancer patients who premenopausal; If the patient had Disease free survival (DFS) of 12 months or more, or if she was diagnosed with metastasis de novo, the recommended first line is either ovarian ablation plus tamoxifen or aromatase inhibitor (Cardoso et al., 2017). For postmenopausal patients aromatase inhibitors are recommended with median progression-free survival (PFS) between 8 and 10 months (Bonneterre et al., 2000) and 10 months (Paridaens et al., 2008).
Chemotherapy regimens that are prescribed in hormone receptor-positive patients includes microtubule inhibitors (including taxanes and vinca alkaloids), anthracyclines, gemcitabine, cyclophosphamide and capecitabine. But endocrinal therapy is preferred as long as the patient is not in visceral crisis (Cardoso et al., 2017).
Recently new drugs that increased progression free survival (PFS) has been approved in the treatment of HR +ve metastatic breast cancer (MBC) as fulvastrant (Selective estrogen receptor modulator) (Ellis et al., 2015) and palbocilib (Ck4/6 inhibitor) (Finn et al., 2015) as first line and eveirolimus (mTor inhibitor)(Pritchard et al., 2012) as second line.
The optimum sequence of endocrinal treatment and chemotherapy has not been fully clarified, It is of great importance to bear in mind that the goal of treatment in recurrent and metastatic breast cancer is extending the progression free survival (PFS) and sustaining a good quality of life (Cardoso et al., 2017).
A retrospective study by Shankar et al. that compared between combination of capecitabine and aromatase inhibitor (AI) versus capecitabine alone versus aromatase inhibitor alone showed that the median PFS of first-line treatment was significantly better for the combination with PFS 21 months vs 8.0 months for capecitabine and 15.0 months for AI. For second-line treatment, the PFS was longer in the combination compared with capecitabine and Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively) (Shankar et al., 2015).
Alvarado et al, compared combination aromatase inhibitor plus capecitabine versus capecitabine alone versus aromatase inhibitor alone. The median PFS of first-line treatment was significantly better for the combination (PFS not-reached for combination vs.3.0 m for capecitabine and 13.0 m for AI, p\<0.0001). For second-line treatment, the PFS was longer in the combination compared to capecitabine and AI (PFS not reached vs. 6.0 m vs.13.0 m, respectively, p=0-041) (Alvarado et al., 2012).
In China a Phase II trial assessed the use of of metronomic oral capecitabine therapy combined with aromatase inhibitors in postmenopausal metastatic and recurrent breast cancer resistant to first-line aromataseinhibitors and the results showed overall Response Rate (ORR) 70.5% and median PFS 9.57 months (L. Jian-wei et al., 2015). Lee S. Schwartzberg conducted a phase II trial which results showed that fulvastrant with metronomic capecitabine for women with HR-Positive, HER2-Negative MBC has Median PFS was 14.98 months (Schwartzberg et al., 2014).
Capecitabine; being cheaper and more available in economically disadvantaged countries together with the promising results of the previous retrospective trial by Shankar et al and the prospective trial by Alvarado Miranda et al ; further confirmation of such results by a prospective randomized clinical trial is crucial. Currently a phase III trial under the title of "Metronomic Capecitabine Plus Aromatase Inhibitor for First Line Treatment in HR(+), Her2(-) Metastatic Breast Cancer" with the primary results expected to be published on 2021 (Sun Yat-sen University, 2016).
