Endocrine Therapy Options Research Articles

Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century

Breast cancer accounts for 33% of all incident cancers in women in North America, and there are an estimated >2 million breast cancer survivors in the United States today. Ovarian hormones are intimately involved in the initiation and promotion of breast cancer development, with targeted endocrine therapies being the most widely used as anticancer treatment. It is not surprising that these treatments frequently cause persistent menopausal symptoms in breast cancer survivors. In addition, adjuvant chemotherapy often induces premature menopause in younger patients with breast cancer. Some women at high risk for the development of breast cancer (e.g., precancerous breast disease, carriers of deleterious hereditary predisposition genes) experience vasomotor symptoms as a result of tamoxifen therapy or preventive oophorectomy. Clinical management of menopausal symptoms in these settings is complicated by the relative prohibition of hormonal therapies and the fact that breast cancer-directed therapies often exacerbate these menopausal symptoms. Thus, this special population of women requires unique management strategies and deserves separate consideration.

Chemotherapy-induced amenorrhea is increased in patients treated with adjuvant doxorubicin and cyclophosphamide (AC) followed by a taxane (T)

651 Background: 25% of invasive breast cancers occur in premenopausal women. Adjuvant chemotherapy may induce amenorrhea, resulting in infertility, influencing hormonal therapy options, and potentially increasing risks of late toxicity. Methods: We retrospectively surveyed women who were premenopausal and < age 50 at initiation of chemotherapy to determine if giving T after AC (AC → T) altered rates of chemotherapy induced amenorrhea (CIA). Women who received either AC x 4 or AC x 4 followed by 3 months of T (either paclitaxel or docetaxel) with or without adjuvant tamoxifen were recruited from a dedicated breast clinic and the Young Survival Coalition. CIA was defined as cessation of menses within one year of starting chemotherapy and lasting ≥ 6 months. Results: 195 eligible patients completed the survey. 160 were ≤ 40. 35 were > 40 but < 50. 77 patients received AC, 118 received AC → T. In patients ≤ 40, the rate of CIA was greater for those who received AC → T (61%) as compared to AC (44%), p=0.04 (OR 1.97, 95% CI 1.01 to 3.84). Many of these young women subsequently resumed menstruating (33% receiving AC, 43% receiving AC → T). Women > 40 had a high likelihood of experiencing CIA with both AC (81%) and AC → T (84%), p=0.35 (95% CI 0.20 to 8.31) and for 82% this was permanent. Results of multivariate logistic regression analysis show that the odds of developing CIA was nearly 5 fold higher for women > 40 than for those ≤ 40 (p=0.002). Those receiving AC → T had an odds ratio of CIA of 1.9 compared to those receiving AC (p=0.05). Tamoxifen did not influence CIA in either group of patients. Conclusion: The addition of T to AC increases the risk of CIA in patients ≤ 40. Women ≤ 40 who experience CIA have a substantial chance of resuming menstruation even after 6 months of amenorrhea and this should be carefully considered when planning hormonal therapy and contraception in this age group. No significant financial relationships to disclose.

Menopausal hormone therapy (HT) in patients with breast cancer

Objectives To assess the effect of menopausal hormone therapy (HT) on reoccurrence, cancer-related mortality, and overall mortality after a diagnosis of breast cancer. Methods We performed a quantitative review of all studies reporting experience with menopausal HT for symptomatic use after a diagnosis of breast cancer. Rates of reoccurrence, cancer-related mortality, and overall mortality were calculated in this entire group. A subgroup analysis was performed in studies using a control population to assess the odds ratio of cancer reoccurrence and mortality in hormone users versus non-users. Results Fifteen studies encompassing 1416 breast cancer survivors using HT were identified. Seven studies included a control group comprised of 1998 patients. Among the 1416 HT users, reoccurrence was noted in 10.0% (95% CI: 8.4–11.6%). Cancer-related mortality occurred at a rate of 2.6% (95% CI: 1.8–3.7%), while overall mortality was 4.5% (95% CI: 3.4–5.8%). Compared to non-users, patients using HT had a decreased chance of reoccurrence and cancer-related mortality with combined odds ratio of 0.5 (95% CI: 0.2–0.7) and 0.3 (95% CI: 0.0–0.6), respectively. Conclusions In our review, menopausal HT use in breast cancer survivors was not associated with increased cancer reoccurrence, cancer-related mortality or total mortality. Despite conflicting opinions on this issue, it is important for primary care physicians to feel comfortable medically managing the increasing number of breast cancer survivors. In the subset of women with severe menopausal symptoms, HT options should be reviewed if non-hormonal methods are ineffective. Future trials should focus on better ways to identify breast cancer survivors who may safely benefit from HT versus those who have a substantial risk of reoccurrence with HT use.

Hormonal therapy options for prostate‐specific antigen‐only recurrence of prostate cancer after previous local therapy

Prostate cancer recurrence that is detectable only by a rise in PSA level after successful local treatment for prostate cancer is a very common problem facing patients and their clinicians. Recent studies suggest that early hormonal therapy provides a survival benefit in patients with M0 disease and after RP in patients with pelvic lymph node metastases; however, the survival benefit for PSA-only recurrence has yet to be confirmed. As shown by the case histories presented here, unconventional hormonal therapy, e.g. antiandrogen monotherapy, appears to be a reasonable option. The potency-sparing potential of this approach is appealing, as is the reduced degree of other side-effects associated with traditional hormonal (castration) therapies, but the long-term efficacy in patients with early PSA-only progression is unknown. The possibility of breast symptoms during antiandrogen monotherapy may be reduced with the use of prophylactic low-dose breast irradiation. More clinical trials are needed to determine the best treatments, alone and in combination, for these patients.

Advances in Endocrine Therapy for Breast Cancer: Considering Efficacy, Safety, and Quality of Life

Breast cancer is the most common cancer found in women in the United States. Endocrine therapy is the standard of care for most women with hormone receptor-positive tumors in adjuvant and metastatic settings. The selective estrogen response modifier tamoxifen has been the standard treatment for postmenopausal patients for many years. Numerous new endocrine therapy agents provide women with novel treatment options, including the nonsteroidal aromatase inhibitors anastrozole and letrozole, the steroidal aromatase inhibitor exemestane, and the estrogen receptor antagonist fulvestrant. Clinical trials have begun to define the role of these agents and their unique side-effect profiles. Nurses are vital in supporting patients in the decision-making process, managing side effects of treatment, and making observations to enhance understanding of the patient experience with new treatments. This article will assist nurses in educating patients about endocrine therapy options and their associated potential short- and long-term side effects, as well as treatment demands.

Hormonal therapy options for patients with a rising prostate-specific antigen level after primary treatment for prostate cancer

At this time, many treatment options exist for primary androgen-deprivation therapy. “Standard” options with long-term results on outcome include orchiectomy, monotherapy with a luteinizing hormone–releasing hormone (LHRH) agonist, and combined androgen blockade using an LHRH agonist and antiandrogen. All treatments are associated with some morbidity related to the reduction of circulating testosterone. For this reason, “alternative” regimens are under active study to determine whether equal outcomes can be achieved with lesser toxicity.

HER2 overexpressing metastatic breast cancer.

More than 40,000 women in the United States die each year from metastatic breast cancer. Elucidation of HER2 and its role in malignant transformation has helped define a subset of aggressive breast cancer that may be relatively resistant to non-anthracycline-based therapies and hormonal agents, but responds to targeted molecular therapy. Trastuzumab, an antibody against HER2, has proven effective as single agent therapy in women with HER2 overexpressed metastatic breast cancer. Moreover, in combination with chemotherapy, trastuzumab has been shown to delay disease progression and improve overall survival for women with HER2-positive advanced breast cancer. The combination of chemotherapy and trastuzumab is emerging as a standard of care in women with HER2 overexpressed metastatic breast cancer. Several combination regimens using trastuzumab with taxanes, vinca alkaloids, or platinum compounds have demonstrated efficacy in first- and second-line treatment settings. However, the development of anthracycline-based combinations has been limited by concerns of related cardiotoxicity. Newer multi-agent regimens are in development. The optimal combination, duration, and sequence of trastuzumab therapy remain unknown in patients with HER2-positive metastatic disease. The role of continuing treatment after disease progression is also unclear. Evidence from some retrospective analyses suggest HER2-positive tumors are relatively resistant to tamoxifen and perhaps more responsive to aromatase inhibitors, although such data are inconclusive. HER2 status should not be used routinely for clinical decision making regarding hormonal therapy options. Several ongoing trials are attempting to address these and other issues related to HER2 testing to select the most appropriate candidates for these emerging therapies. While many questions remain, the treatment of HER2 overexpressing metastatic breast cancer is rapidly evolving, and represents a new approach to treatment in oncology.

Proper sequence of endocrine therapies in advanced breast cancer.

Tamoxifen (TAM) is widely used as therapy in early breast cancer and first-line endocrine therapy in metastatic disease. Despite this therapy, many patients relapse and an important question is: What is the preferred sequence of endocrine therapies in metastatic breast cancer (MBC). While treatment with oophorectomy, aminoglutethimide or progestins have been a logical choice after failure to Tamoxifen recent research has extended the options for endocrine therapy of MBC. New selective aromatase inhibitors (AI) are now in clinical use. The first commercially available of these inhibitors is LENTARON. The active ingredient of LENTARON is a steroidal compound 4-OH-androstenedione: Formestane. It is presented as a depot formulation and applied as an i.m. injection of 250 mg every second week. Previous findings from phase II trials have indicated similar activity as other endocrine treatment modalities. Clinical investigations in properly conducted phase III trials have revealed that the efficacy of LENTARON matches the results which can be obtained with TAM and Megace in trials of first and second-line endocrine therapy. Fifty-four and 51% of MBC patients, respectively, did benefit from therapy with LENTARON in these phase III trials by achieving objective responses or stable disease. Moreover, similar overall survival was seen. The systemic tolerability of LENTARON is comparable to that of TAM, and LENTARON seems less systemically toxic than Megace. Local side effects occured in approximately 7% of the patients giving rise mainly to pain or inflammation at the injection site. In elderly patients, LENTARON therapy assures compliance and no interference with other oral medications has been observed. In conclusion, since the endocrine treatment modalities are comparable in terms of efficacy the optimal sequence of these treatments is based upon differences in tolerability. Patients previously treated with Tamoxifen and with a high probability of a further endocrine response could preferably be treated with a selective AI like LENTARON as second-line endocrine therapy followed by a progestin upon progression in responders.