Background: The genitourinary syndrome of menopause (GSM) and particularly vulvo-vaginal atrophy (VVA) is a frequent complaint among breast cancer (BC) survivors that lead to an important affection of their quality of life (QoL). Lifestyle measures such as smoking cessation or regular sexual activity are usually insufficient to significantly improve GSM and related symptoms such VVA and although some therapies as lubricants and polycarbophil moisturized gels are considered first-line therapies to alleviate symptoms of VVA, these non-hormonal options are not able to reverse atrophy once it occurs. Instead, this complaint is corrected by local estrogens. The estrogen vaginal treatment usually used to treat GSM, is an issue of concern in this group due to the possible negative effect over the BC outcomes. On the other hand, the worsening of QoL in these patients due to symptoms related to GSM can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly. Results: A Cochrane review of 30 randomized controlled trials including 6235 postmenopausal women, showed that the different forms of local estrogenic preparations appeared to be equally effective for relieving the symptoms of VVA and a higher proportion of these women reported improvement in symptoms compared to those who received placebo. A few clinical studies have documented a systemic absorption after vaginal estrogen administration in BC patients. However, if this absorption could affect the BC, outcome is still controversial, and the available evidence of local hormone therapy in BC patients, although has not demonstrated a negative effect, it is not possible to draw any firm conclusions. Promestriene, an estrogen analogue, is an effective treatment to relief the symptoms of VVA in BC patients with a very poorly vaginal absorption. Furthermore, the absence of a systemic effect of promestriene has been confirmed and even after up to 4–6 months of therapeutic doses in clinical studies that included women with estrogen sensitive malignancies. Conclusions:The beneficial effects of vaginal estrogen therapy for women with GSM without response to non-hormonal therapies could outweigh the risks and provide an overall improvement in QoL. Alternatives as promestriene and ospemifene must be considered as a better choice, although knowing that still lack evidence of long-term safety in patients with BC.