The findings from both qualitative and quantitative analysis of studies on performing BC surgery in a certain phase of the menstrual cycle are unclear. In the good phase of the menstrual cycle (Days 0 − 2 and 13–32), women with ER (+) tumors have a significantly better outcome than those with ER (-) tumors and follicular phase surgery is associated with a poor prognosis regardless of hormone status [11].
The current study was set to investigate the importance of adjusting the timing of surgery whether the effect of menstrual cycle phase on the axillary lymph node, ER, PR and c-erbB-2 gene in patients with premenopausal breast tumors. The number of metastatic axillary lymph nodes in the luteal phase was significantly lower in women with BC than in the follicular phase.
A specific breast phenotype with lack of ER, PR, and c-erbB-2 expression, the so-called ‘‘triple-negative’’ phenotype, is linked with poor prognosis [13]. In the light of the data in the literature, this study was set to investigate whether the effect of menstrual cycle phase on the axillary lymph node, ER, PR and c-erbB-2 gene in patients with premenopausal breast tumors. It is concluded that prognostic factors are better in patients with luteal phase. In this way, we believe that luteal phase can be used to determine the operation time for women in premenopausal period. With the mentioned study is a study feature will be the first time in Turkey.
The development and clinical course of BC is modulated by various endocrine effects. It is now widely recognized that endocrine interventions represent the most effective approaches for reducing the risk of recurrence and death for hormone-responsive primary breast cancer and reducing patients at risk of developing this disease. In the last 30 years, some hypotheses have been established on the basis of the endocrine-cancer relationship, and although many have been proven, there are still hypotheses awaiting clarification.
There is still discordance between studies and well-conducted prospective studies have provided evidence, both for and against, rescheduling surgery to the luteal phase [14]. Our study demonstrates that, the number of metastatic axillary lymph nodes in the luteal phase was significantly lower in women with BC than in the follicular phase. ER positivity, PR positivity and c-erb B2 negativity were higher in the luteal phase than follicular phase. These results show that prognostic criteria are well observed in luteal phase. One of these hypotheses was proposed by Hrushesky et al. [15] in 1989 and they suggested the concept of surgical intervention to treat BC in premenopausal women according to the stage of the menstrual cycle. The authors suggested that premenopausal patients with BC who were operated during the perimenstrual period of the menstrual cycle had higher disease-free and overall survival rates compared to patients operated in other phases of the cycle [5]. However, according to the results of the retrospective, prospective and meta-analysis studies performed on this hypothesis for the last three decades; while some studies [5, 16] support Hrushesky et al. [15], there are studies reporting that the menstrual cycle does not affect the outcome [17, 18], or that the opposite results (patients who underwent surgical treatment in the follicular phase are better than those receiving luteal phase surgery) [19].
Continuous fluctuations of estrogen and progesterone throughout the reproductive period in women affect the phenotype and function of breast, stromal and immune cells including macrophages and regulatory T cells, as well as the turnover of the mammary epithelium, stem cells, and extracellular matrix. Collectively, these events can lead to genome instability, increase the likelihood of random genetic mutations, reduce immune supervision and increase tolerance in the mammary gland; thus increasing the risk of breast cancer onset [20]. In addition, fluctuations in estrogen and progesterone throughout the menstrual cycle direct the proliferation, differentiation and apoptosis in the mammary gland epithelium [21]. Menstrual cycle phases in women; Pituitary gland hormones, follicle stimulating hormone and luteinizing hormone and ovarian hormones are regulated by fluctuations in estrogen and progesterone. Estrogen exerts proliferative effects on mammary epithelial channels by direct ERs, as well as up-regulates the expression of PR during the luteal phase of the cycle [20]. ER, PR and c-ERBB2 (HER-2/neu) are important therapeutic and prognostic markers for breast carcinoma [22]. Vasei et al. [23] showed that the ER and PR are higher in the luteal phase. In another study, they reported that ER positivity was higher in the follicular phase and the PR was found to be independent of the menstrual cycle; and if the condition of the hormone receptor is found to be negative, it is necessary to reevaluate the phase of the menstrual cycle in which the operation is performed [24]. Liu et al. [25] reported that surgery performed during the follicular phase provides a more favorable prognosis compared with the luteal phase.
Our study suggests that BC surgery during the luteal phase in pre-menopausal women is associated with a better clinical outcome. Although larger-scale studies are needed, our results suggest that better results can be achieved by performing surgery in luteal phase in BC patients during premenopausal period. Prospective randomized clinical trials are also necessary to determine the full extent of survival benefits of luteal surgical timing.