Breast cancer ovarian function inhibition (OFS) is right and wrong in breast cancer.

In China, 50% to 60% of the hormone receptors in premenopausal women are positive, and complementary endocrine therapy is an important means to reduce the risk of recurrence in such patients, such as the treatment of tamoxifen for 5 to 10 years has become the standard endocrine treatment for patients with premenopausal hormone receptor-positive early breast cancer"Further reducing estrogen levels in young breast cancer patients can be transformed into survival improvement" has been a hot topic of research on endocrine therapy in premenopausal patientsRetrospective analysis of assisted clinical trials such as MA5, NSABP B30 and ZEBRA found that younger patients had a better prognosis than those without amenorrhea if they had amenorrhea after chemotherapyThis raises the hypothesis that artificial ovarian function suppression can improve the prognosisThe Meta analysis by Cuzick et alfound that the risk of recurrence could be further reduced in premenopausal patients, especially those younger than 40 years of age, whether combined with ovarian function inhibition on the basis of chemotherapy or endocrine therapyHowever, small sample studies, retrospective studies, or Meta analysis on this basis do not provide enough evidence-based medical evidence to guide clinical practiceAt the same time, the researchers also observed in some clinical studies, the younger patients, the lower the probability of chemotherapy amenorrhea, after chemotherapy ovarian function recovery rate is higher, the poorer the prognosis than patients without amenorrheaSo there is no definitive answer as to which patients should inhibit the function of the joint ovary, how long the joint, and whether the prognosis will benefitFirst, OFS mode and choice Ofsp breast cancer is estrogen-dependent cancer, premenopausal breast cancer development and recurrence metastasis and the existence of ovarian function and endocrine level secloseOvarian function suppression (OFS) was the first major strategy for endocrine therapy for premenopausal hormone receptor-positive (HR-) breast cancer, including ovarian excision, ovarian radiotherapy, and gnRHaRadiotherapy deposition: ovarian local radiotherapy, the overall effect and success rate is inferior to the surgical deposition, the permanent loss of ovarian functiondrug de-potential: rapid reduction of serum estrogen levels, to achieve postmenopausal status, after discontinuation to a certain extent reversibleSurgical de-seiscing includes traditional surgical excision and laparoscopic surgery, which are invasive and irreversibleAlthough the ovarian excision can cause a rapid reduction in serum E2 concentration, the patient also permanently loses the ovariesSurgical removal of the ovaries takes a faster time, takes effect more than 1 month, and is more reliable and thoroughIt also reduces the risk of ovarian cancer, especially for those at high riskHowever, ovarian surgery can lead to irreversible premature menopause, which can lead to a series of adverse reactions, such as osteoporosis, increased risk of cardiovascular disease and permanent loss of fertility, so young patients should be careful when performing ovarian surgeryRadiation degeneration is more applicable to patients who are weak and cannot tolerate surgery, but the effect is slow, generally 6 to 8 weeks, the dose of radiation deposition should be given to 20Gy within 10 daysOvarian radiation deity is easier to implement in clinical practice and has low cost, but its efficacy is related to factors such as radiation dose, dose segmentation method, target area design and patient's ageThe disadvantage of radiation de-potential is that the effect time is longer, generally takes 6 to 8 weeks, there may be incomplete de-potentialAnd pelvic radiation therapy may have adverse reactions to long-term radiotherapyOvarian radiotherapy-related studies showed that 20% to 30% of patients after radiotherapy could not successfully achieve the effect of ovarian de-conditioning, and the overall level of induced estrogen decline significantly worse than ovarian excision, so clinical use was limitedThe desorpherining drug GnRHa inhibits estrogen levels in the serum to a degree similar to surgical deactivityIntergroup studies in hormone-receptor-positive metastatic breast cancer patients have shown that Goscherin is as effective as surgery in breast cancer treatment, and that patients with Goschererin have good safety and toleranceIn the ZEBRA study of complementary therapy, 77 percent of patients who received two years of goschererin-assisted therapy regained ovarian function within three years, compared with 23 percent of patients who received CMF chemotherapy within three yearsTherefore, GnRHa is an ideal OFS method for premenopausal breast cancer patients, and the 2016 ASCO guidelines update on OFS are also recommended as the first choice for OFS therapyOfs Beneficiaries Recently, with the publication of the results of clinical trials of S O F T and T E X T, there is a new evidence-based medical basis in this areaSOFT studied nearly 3,047 premenopausal early menopausal breast cancer patients, and randomly received ovarian function-suppressing combined TAM or aromatase inhibitor (Aromatase inhibitor, AI) compared the standard single drug TAM, with a duration of 5 yearsThe TEXT study compared differences between ovarian function inhibition combined with TAM or AI in 2,672 premenopausal patientsSOFT study found that ovarian function inhibition combined AI reduced the risk of breast cancer recurrence by 36% compared to single drug TAM, its 5-year breast cancer-free survival rate of more than 90%, especially in patients who received chemotherapy, its 5-year breast cancer-free survival absolute benefit rate of 7.7%, no distance metastasis absolute benefit of 4.2%, these survival benefits are more significant in younger patients younger than 35 years of ageThe combined analysis of SOFT and TEXT also showed that the five-year disease-free survival rate of the ovarian function-suppressing joint AI relative to ovarian function inhibition of the joint TAM was 91.1% and 87.3%, respectively, and the absolute benefit rate was 3.8% (HR-0.72, P-0.000 2)In patients without chemotherapy, the overall prognosis was very low, and the difference in different endocrine therapy strategies was not statistically significant (P.05) Based on these findings, more and more physicians at the assisted treatment stage will recommend a combination of ovarian function inhibition in premenopausal patients, especially in younger patients, or those who have not amenorrhea after chemotherapy 2015 St Gallen Expert Consensus Recommends that considerations in support of joint ovarian function inhibition are: age : 35 years (81%), recovery of premenopausal hormone levels after assisted chemotherapy (73.7%), hemic classification of 3 (55.9%), s4 lymph node metastasis (89.7%), multi-gene tests show poor prognosis (60%) and 56.7% support ovarian function inhibition for 5 years The proportion of women in our country who have late marriage and late childbearing is higher, and many young patients develop breast cancer before they have given birth It is essential to protect ovarian function in this part of the patient, so that they can retain fertility function as much as possible while receiving breast cancer treatment Chemotherapy damages mature follicle cells, inhibits the formation of raw follicle follicles, causes irreversible damage to ovarian function, affects menstrual cycle and even leads to early ovarian failure In foreign countries, patients with fertility requirements usually consult obstetrics and gynecology departments before chemotherapy, oocyte freezing, but in our country for various reasons, this freezing technology is rarely used This is especially important for most breast cancer clinicians to adopt GnRHa for ovarian function protection In 2015, St Gallen experts recommended that young breast cancer patients, regardless of whether they are hormone-receptor-positive or negative, should be treated with chemotherapy while being given additional ovarian function inhibition for reproductive function protection of the preferred way of OFS: gnRHa breast cancer is estrogen-dependent cancer, premenopausal breast cancer development and recurrent metastasis and the existence of ovarian function and endocrine levels are closely related Ovarian function inhibition (OFS) was the first major strategy for endocrine therapy for premenopausal hormone receptor-positive (HR-) breast cancer, including ovarian excision, ovarian radiotherapy and the drug GnRHa Among them, surgical removal of the ovaries although can quickly reduce serum E2 concentration, but irreversible, the patient will permanently lose the ovaries For young patients, caution should be given, as ovarian removal can lead to premature menopause, loss of fertility, and a range of adverse reactions such as cardiovascular disease and osteoporosis Radiotherapy is also an irreversible way, suitable for patients with weak physique and undertolerance of surgery, but the effect is not as good as ovarian excision, there is the disadvantage of incomplete de-conditioning, so clinical use is limited The drug GnRHa is a reversible way, represented by progesterone-free hormone release hormone (LHRHa) analogues, which significantly suppresses estrogen levels in the serum to a degree similar to surgical degeneration, and gradually restores ovarian function after suspension As a result, GnRHa has gradually become the preferred OFS for premenopausal breast cancer patients GnRHa represents drugs including Goscherin, Quprelin and Liang pririn, which are currently on the market, including Goscherin and Liang pririn Intergroup studies show that Goscherin and ovary removal of FFS are similar to OS and good tolerance and safety, and the results of several clinical studies such as INT-0101, ZIPP and ABCSG12 show that endocrine therapy is an important treatment for HR-plus early breast cancer, and Goscherin is a commonly used drug for endocrine therapy Second, the change of THE history of OFS As early as 1889, German surgeon Thomas William Nunn noticed that a postmenopausal female breast cancer patient seisdegradable tumor degeneration, and therefore proposed the implementation of bilateral ovary removal induced menopause, further induced tumor degeneration On June 15, 1895, British doctor George Thomas Beatson performed the world's first ovarian ectomy on a 33-year-old woman with advanced breast cancer, who survived for nearly four years Beatson reported the following year on Lancet that ovarian removal surgery could successfully treat advanced breast cancer and that the results could be repeated, causing a stir Since then, the curtain on endocrine therapy for breast cancer has been slowly opened In 1904, France's Foveau de Courmelles first used ovarian de-altrusis as an alternative to surgical de-seismology, which was also an innovation at the time However, ovarian radiotherapy-related studies show that 20% to 30% of patients after radiotherapy can not successfully achieve the effect of ovarian de-conditioning, and the overall level of induced estrogen decline significantly worse than ovarian excision, so clinical use is limited Then there is the emergence of GnRHa-type drugs, because gnRHa drugs have few damage, low side effects, and the inhibition of ovarian function to a certain extent reversible, become an important means of endocrine treatment of premenopausal breast cancer, but also the preferred WAY of OFS treatment However, when it comes to endocrine drugs for breast cancer, it has to be mentioned that tamoxifen (tamoxifen, TAM) In 1972, TAM father Virgil Craig Jordan began studying TAM's blocking effect on estrogen receptors (estrogen receptor, ER) into breast cancer treatment, and in December 1977, the U.S FDA approved TAM for breast cancer treatment, which became a mainstream drug in endocrine therapy because of oral ease and relatively low adverse event rates, which are more popular than ovarian surgery or radiotherapy 3 OFS-related clinical research: yes and no for premenopausal early-stage breast cancer patients, OFS treatment has been in the breast cancer assistive treatment for decades of exploration history, such as THE ABC (OAS) study, ABCSG-12 study and INT-0101 research For the overall population analysis, OFS co-use did not improve overall treatment outcomes, but in subgroup analysis, it was found that patients who were relatively young (35 years of age) or without amenorrhea/ovary function were still in good condition after chemotherapy (i.e., higher estrogen levels) may have some benefit Although these subgroup results affected clinical practice, they did not receive a particularly high level of evidence-based medical recommendations until the emergence of the SOFT and TEXT study In 2014, SOFT study data showed that for the overall population analysis, premenopausal patients were unable to benefit from OFS in combination with tamoxifen (TAM)/aromatase inhibitor (AI) treatment, withno significant differences in statistics; OfS (in high-risk patients) can reduce recurrence, and the results of a 5.7-year combined follow-up study in THE SOFT and TEXT study showed that OFS-AI significantly improved the disease-free survival rate (DFS) in premenopausal HR-breast cancer patients compared to OFS-Tam Until the SABCS meeting in December 2017, the results of the 8 years follow-up results of THE SOFT study were announced, and the 8 years of DFS in the TAM, OFS-TAM, OFS-AI groups were 78.9%, 83.2% and 85.9%, respectively, and the overall population benefited from THE use of OFS therapy It reverses the previous perception that the overall population cannot benefit from OFS, while the median follow-up data from SOFT and TEXT joint analysis for 9 years were also published, and the benefits of OFS-AI continued to increase, with 86.8% vs 82.8% in 8 years Based on the latest research results, we can see the survival benefits of OFS therapy, and confirm that the combined OFS treatment can bring overall benefits to low- and middle-risk patients 4 OFS beneficiaries: Middle- and high-risk premenopausal patients based on the results of multiple clinical studies, there is growing evidence that the use of a combination of OFS treatment can be more beneficial for premenopausal breast cancer patients, especially those who are young or who have not amenorresises after chemotherapy The Consensus of Experts in Clinical Applications of Early Breast Cancer in China (2016 Edition) shows that high-risk premenopausal hormone-receptor-positive breast cancer is recommended for endocrine therapy containing OFS, and patients with medium-risk risk should be considered for use, while FORS treatment is not recommended for patients with low risk in addition, the 2017 St Gallen expert consensus noted that the considerations in support of joint OFS therapy were: age of 35, recovery of premenopausal hormone levels after complementary chemotherapy, s4 lymph node metastasis, and poor prognosis from multi-gene testing In the latest CSCO 2018 edition of the expert consensus, low-risk patients recommend the application of single-drug triamcinolone, moderate-risk patients can consider the use of OFS-TAM scenarios, and high-risk patients are generally recommended OFS-AI strategy V OfS (GnRHa) best time and treatment: there is still controversy, no conclusive for premenopausal early HR-breast cancer patients receiving chemotherapy, the timing of the use of GnRHa has been controversial, is the end of synchronous chemotherapy or chemotherapy and confirm the re-use of menopause status? The astrRA study, presented at the 2018 ASCO conference, found that more than 90 percent of patients recovered from ovarian function within two years of the end of chemotherapy, and excessive waiting would result in some patients losing access to OFS treatment Based on TEXT.