Significance of Ovarian Function Suppression in Endocrine Therapy for Breast Cancer in Pre-Menopausal Women

Abstract

Ovarian function suppression (OFS) for treating breast cancer in pre-menopausal women was introduced for the first time in the late 19th century as bilateral oophorectomy. It was not until the 1960s that the oestrogen receptor was identified and a test for detecting endocrine sensitivity of the breast cancer was developed. A weakness of early trials on OFS for breast cancer treatment is therefore their failure to take receptor sensitivity into account when selecting participants. A meta-analysis performed in the early 1990s first proved that adjuvant OFS significantly improved the cure rate of oestrogen receptor-positive breast cancer in pre-menopausal women regardless of whether it was carried out through oophorectomy, radiation-induced ablation or drug therapy. In the 1970s, tamoxifen was synthesized. It became one of the most important cancer drugs and today constitutes the gold standard for endocrine adjuvant therapy. Taking tamoxifen for a five-year period lowers mortality by 30?% over 15 years. Ten years of tamoxifen therapy reduces mortality even further, with increased side effects, however. Research over the past ten years has proven that for post-menopausal women, aromatase inhibitors have benefits over tamoxifen. Current trial results have rekindled the debate about the combination of OFS with tamoxifen or with aromatase inhibitors for adjuvant breast cancer treatment of pre-menopausal women. These trials have reported an improvement in disease-free survival in patients with a high risk of recurrence when they are treated with a combination of OFS plus tamoxifen or aromatase inhibitors, especially in women younger than 35. However, combination therapy causes significantly more side effects, which could negatively impact compliance. Endocrine treatments administered over a period of many years show waning compliance, which tends to be only around 50?% after five years. Inadequate compliance compromises efficacy and increases the risk of mortality. For this reason, when indicating and supporting endocrine adjuvant therapy, physicians must ensure that compliance will be good. To prevent recurrence in the long run, it is much more effective to prescribe a somewhat less effective therapy that will actually be carried out than to prescribe one that is theoretically more effective, but is not adhered to consistently.

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

“…There is an important difference between these compounds, as antagonists block estrogen action in all tissues, while SERMs can act as agonists in certain tissues, and as antagonists in other tissues, where their actions depend on the availability of co-activators and co-repressors (Traboulsi et al, 2017 ). The best studied SERM is tamoxifen, which has been successfully applied in the treatment of hormone-receptor-positive breast cancer for more than 40 years (see Scharl and Salterberg, 2016 ). In endometrium, tamoxifen has estrogenic effects and stimulates cell proliferation, which leads to hyperplasia, and eventually, to endometrial cancer (Ellis et al, 2015 ).…”

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients

“…However, AIs are known to induce musculoskeletal pain as one of the main side effects [ [9] , [10] , [11] , [12] , [13] ], so that patients often become noncompliant [ 11 ] and discontinue treatment [ 9 , [12] , [13] , [14] , [15] ]. Noncompliance and early cessation of treatment in turn lead to a poorer prognosis [ 12 , 16 ] — emphasizing the importance of maintaining patients’ compliance and persistence.…”

Time-resolved profiling reveals ATF3 as a novel mediator of endocrine resistance in breast cancer

“…One unexpected result was the lack of growth 495 inhibition of WT cells in the LET treated group. This could be explained by the adverse effects 496 LET has on pre-menopausal women: the reduction in the peripheral E2 levels activates the 497 hypothalamic-pituitary axis; this increases gonadotropin secretion, which stimulates the 498 ovaries, resulting in increased E2 production 59 . Therefore LET might have stimulated E2 499 production to levels sufficient to sustain the growth of MCF7 WT, while these might still not be 500 high enough to support the growth of the ATF3 knockout clones that show a delayed tumor 501 growth.…”