There are approximately 6,500 new cases of breast cancer diagnosed per year in Taiwanese women, and most are younger in age and more likely to be premenopausal than their Western counterparts [19
]. A recent report indicated that > 50% of the total breast cancer cases annually in Taiwan and China are in premenopausal patients [19
]. In order to maintain QoL and fertility, protection of ovarian function is crucial for women undergoing breast cancer therapy.
LHRH analogues decrease ovarian estradiol production indirectly by impinging on the hypothalamic-pituitary-ovarian axis, and inhibiting secretion of pituitary gonadotrophins [2
]. Chemotherapy usually results in gonado-toxicity and induces damage of ovarian function. Goserelin has been observed to protect ovarian function; therefore, it is unlikely to induce premature menopause and osteoporosis in young women [1
]. In a phase II pilot study, the addition of goserelin to adjuvant therapy of premenopausal patients with early breast cancer was well tolerated and shown to protect ovarian function [3
]. In our study, 86% of patients who were treated with goserelin resumed normal menses, and 1 patient had a pregnancy that ended with a normal childbirth 5 years after treatment.
The present study evaluated the cost-effectiveness of adjuvant goserelin therapy versus adjuvant chemotherapy in premenopausal breast cancer patients with stage Ia to IIIa disease. To our knowledge, this is the first study evaluating the integration of goserelin into adjuvant hormonal therapy in premenopausal breast cancer. An illuminating study exploring women's treatment preferences found that when healthy, premenopausal women were given the choice of adjuvant goserelin or CMF chemotherapy upon hypothetically developing ER + breast cancer, an overwhelming number chose goserelin over chemotherapy [20
]. The primary reasons for choosing goserelin were to avoid the general side effects of chemotherapy, in particular hair loss, and a lesser disruption of the activities of normal life with goserelin as compared to chemotherapy. Other factors such as fertility, length of treatment, and amount of travel required to receive treatments were discussed in the study; however, no comments regarding the cost of treatment were made.
The results of our study indicate that goserelin is particularly cost-effective compared to TE and TEC chemotherapy regimens, and comparable to CMF and FEC. The cost of 2-year goserelin therapy appears more expensive ($5,273 USD) than both CMF (approximately $1,666 USD) and FEC (approximately $1,872), regardless of BSA, but higher QALY is seen. Based on the EORTC-QLQ-CL30 scores from our study, patients who receive goserelin therapy have higher QoL. Similarly, there are positive ICERs for goserelin vs. CMF and FEC, but negative ICERs for goserelin vs. TE and TEC.
There have been 4 large multi-center studies comparing efficacy outcomes between adjuvant goserelin (3.6 mg depot) and adjuvant chemotherapy. These are the German Adjuvant Breast Cancer Group (GABG) trial IV-A-93 [21
], the Austrian Breast and Colorectal Cancer Study Group Trial 5 (ABCSG) [22
], the International Breast Cancer Study Group (IBCSG) Trial VIII [7
], and the Zoladex Early Breast Cancer Research Association Trialists' Group (ZEBRA) [6
]. Of these, the IBCSG trial VIII, ABCSG trial VI, and ZEBRA examined CMF for 6 cycles (28 days each), whereas the GABG trial IV-A-93 examined intravenous cyclophosphamide.
The ZEBRA study [6
], the largest, consisted of primarily ER + patients (1189/1614, 73.7%,) and demonstrated comparable recurrence-free survival, overall survival, and frequency of adverse effects at 6 years for ER + patients, but not for ER- and ER-unknown status patients, a trend seen in the other trials. The IBCSG and ZEBRA trials also indicated significantly better QoL during the first year in patients receiving goserelin, but little difference thereafter [6
]. The ABCSG trial concluded that goserelin and tamoxifen were significantly more effective, with increased local recurrence-free survival and relapse-free survival as compared to CMF premenopausal women with stage I and II breast cancer [22
]. An update on the ZEBRA study at a median follow-up of 7.3 years confirmed the previously reported outcomes for overall survival, and demonstrated the effectiveness of goserelin as an alternative to CMF for adjuvant therapy of premenopausal ER + women with early breast cancer [24
Taken together, the results of the aforementioned trials are consistent with the present finding that adjuvant CMF and FEC produced comparative HRQoL utility values (0.81 vs. 0.78) at last follow-up, and appeared more economically sound than goserelin, in premenopausal patients with early stage breast cancer. It should be noted, however, that although the cost of goserelin may seem exorbitant relative to CMF and FEC, hormonal therapy administered in the early stages of breast cancer is likely to be economical when considering the outcomes of other common medical interventions.
While no cost-utility studies exist on adjuvant goserelin therapy in breast cancer alone, analyses of CMF and FEC have been extensively reported. Total costs of adjuvant CMF therapy in breast cancer have been reported to be approximately $3,852 USD-$10,197 USD (for 9 cycles) in Norway 1998-2000 [25
], which amounts to approximately $1,688 USD per life-year saved in the US in the year 1992 [26
], with drug costs accounting for 40% in both cases. CMF (for 6 cycles) in the present study is the most affordable regimen (approximately $1,788 USD for a BSA of 1.5 m2
and $1,795 USD for a BSA of 1.8 m2
), and differences in costs may likely reflect differences in national costs, rather than any major differences in treatment regimen.
Our review of prior economic evaluation research related to breast cancer treatment revealed the first cost-benefit analysis report discussing post-surgery adjuvant therapy for breast cancer was published in the early 1990s [27
]. In the evaluation report comparing tamoxifen, chemotherapy, and combination therapy, Smith analyzed treatments that were suitable for different disease symptoms in patients with breast cancer > 45 years old and before menopause. The authors concluded that in premenopausal early-stage breast cancer, chemotherapy adds substantial clinical benefit at a modest cost while tamoxifen alone adds meaningful benefit only in ER + cancer, and that combined therapy is effective for all women, but is most beneficial and only cost-effective in ER + women.
Several reports evaluating the cost-benefit of chemotherapy for breast cancer exist in the literature. One report analyzing node positive breast cancer patients and comparing the cost-benefit ratio with/without CMF as adjuvant therapy revealed an ICER value of approximately $447 USD per person, per year [28
]. Another study comparing the cost-benefit of 2 combination therapies, TAC (docetaxel, doxorubicin, and cyclophosphamide) and FAC (fluorouracil, doxorubicin, and cyclophosphamide), utilized a decision-making model from the England National Health Service [29
]. The result showed that when using FAC as a standard, for an increase of 1 unit of TAC per person, per year, the corresponding cost was £15,418, while for an increase of 1 unit of QALY, the corresponding cost was £18,188.
The present study has a number of limitations. First, using multi-attribute utility analysis may have resulted in an overestimated VS before power conversion into an SG score. Also, robustness of the utility analysis could not be ascertained, as a sensitivity analysis was not performed. Second, the results reflect the NHI system of Taiwan. Thus, when estimating costs, total medical costs (surgical intervention, drugs, and other health care services) were assessed from a payer's perspective, and based on standard claims submitted to the NHI. However, the NHI has restrictions on the prescribing of goserelin. Prescription of goserelin requires pre-registry, and is limited to patients who are unsuitable for hysterectomy, or fail to respond to other hormone therapy (e.g., tamoxifen, megestrol). Therefore, goserelin is considered a second line therapeutic agent. Additionally, the cost data that was utilized reflects the Taiwanese societal perspective. Thus, cost-utility thresholds employed in other countries cannot be directly applied. Lastly, because the data retrieved was from the time period of 1993 to 2007, there was a large amount of missing data with respect to patient characteristics, thus we only presented the data set that was complete, age.