Challenges in the endocrine management of breast cancer

The goal of endocrine therapy in breast cancer is to block the action of estrogen on the tumor cells either by inhibiting estrogen from binding to the specific estrogen receptor or by inhibiting its synthesis. Tamoxifen, a selective estrogen receptor modulator, is the standard endocrine treatment for hormone receptor-positive breast cancer, both in the adjuvant and metastatic settings. Tamoxifen inhibits the binding of estrogen to the receptor, resulting in inhibition of hormone action. However, as tamoxifen is also weakly estrogenic, it may not be optimally effective and increases the risk of endometrial cancer and stroke. Furthermore, patients may be refractory or may become resistant to tamoxifen treatment. Since aromatase inhibitors (AI) block the synthesis of estrogen and have no intrinsic estrogenic activity, they have the potential to be more effective than tamoxifen. Their different mechanism of action and chemical structures may also circumvent tamoxifen resistance. Consequently, AIs are currently being evaluated as an alternative to tamoxifen treatment. A preclinical model has recently been developed to compare the efficacy of AIs and antiestrogens in different treatment schemes and to assist in the design of clinical trials. Current studies with the MCF-7Ca xenograft model are exploring the effects of combination and sequential therapy on tumor growth. The efficacy of AIs in the treatment of hormone receptor-positive breast cancer was first demonstrated in five multicenter second-line trials enrolling several hundreds of postmenopausal patients with metastatic breast cancer who had failed tamoxifen treatment. More recently, anastrozole demonstrated efficacy at least equivalent to that of tamoxifen in first-line randomized, phase III clinical trials in postmenopausal women with hormone receptor-positive or unknown metastatic breast cancer, whereas letrozole demonstrated superiority. The steroidal AI exemestane is currently under evaluation. Letrozole is the only AI to have been studied in a randomized, phase III trial in the neoadjuvant setting. In this trial, more patients underwent breast-conserving surgery with letrozole than with tamoxifen. Smaller phase II studies also suggest that both anastrozole and exemestane are active in the neoadjuvant setting. Because neoadjuvant trials permit temporal sampling of breast tissue, substudies in the phase III trial with letrozole have examined the impact of such biomarkers as estrogen receptor, progesterone receptor and epidermal growth factor receptor family members, HER-1 and HER-2, on patient response. AIs are currently under evaluation in the adjuvant setting, and preliminary results of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial have been reported. AIs have proven as safe as tamoxifen in trials in patients with metastatic breast cancer. Ongoing clinical trials in the adjuvant setting include companion studies of end-organ effects, particularly bone metabolism and lipid metabolism evaluations. Quality-of-life assessments are also parts of major clinical trials. A head-to-head quality-of-life assessment of anastrozole compared with letrozole demonstrated patient preference for letrozole. These assessments also clearly indicated the eagerness of patients to participate actively in treatment decisions     

The impact of hormone receptor status on the clinical efficacy of the new-generation aromatase inhibitors: a review of data from first-line metastatic disease trials in postmenopausal women

Hormone receptor status has long been considered important in predicting the efficacy of endocrine agents for the treatment of breast cancer. We aim to address whether hormone receptor status influences treatment outcome in postmenopausal women receiving aromatase inhibitors for advanced breast cancer. We include data from three phase III clinical trials, comparing the activity of the new-generation aromatase inhibitors, anastrozole or letrozole, with tamoxifen as a first-line treatment. For both agents, a significant relationship was observed between hormone receptor status and time to disease progression (TTP), with increased TTP seen in patients with a higher confirmed percentage of estrogen receptor (ER)- and/or progesterone receptor (PR)-positive tumors. A relationship between objective response rate (complete or partial response) or clinical benefit (complete or partial response or stabilization for > or =24 weeks) and hormone receptor status was apparent for anastrozole but not letrozole treatment. Overall these data confirm that hormone receptor status should be a strong consideration in the selection of endocrine treatment for postmenopausal women with advanced breast cancer.     

Are all aromatase inhibitors the same? A review of the current evidence

Third-generation aromatase inhibitors (AIs)--letrozole, anastrozole, and exemestane--are challenging tamoxifen as the standard endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer. AIs suppress estrogen levels by inhibiting aromatase, the enzyme that catalyzes the final step of estrogen biosynthesis. Studies have shown that AIs are highly effective and safe in the treatment of advanced disease, and more recently, AIs have shown promise in the neoadjuvant, adjuvant, and extended adjuvant settings. However, all AIs are not equal. In direct comparisons with anastrozole, letrozole has demonstrated superior estrogen suppression and clinical response in patients with advanced metastatic breast cancer. In addition, letrozole is the only AI to demonstrate consistent superiority over tamoxifen in the neoadjuvant and first-line advanced breast cancer settings. This publication summarizes the available evidence for the efficacy of all 3 agents throughout the breast cancer continuum.     

Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer

With the aromatase inhibitors (AIs) replacing tamoxifen as the first-line treatment for postmenopausal women with hormone receptor-positive early and advanced breast cancer, there is a need to evaluate appropriate endocrine treatment options following AI failure. However, until recently, there were no Phase III trial data in this area. Fulvestrant (Faslodex) is an oestrogen receptor antagonist utilised for the treatment of postmenopausal women with locally advanced or metastatic breast cancer following progression or recurrence on anti-oestrogen therapy. Fulvestrant has a mode of action that is distinct from the AIs and the selective oestrogen receptor modulators, and thus may offer an effective treatment option in the post-AI setting. The Evaluation of Faslodex and Exemestane Clinical Trial (EFECT) is the first Phase III trial to evaluate the efficacy and tolerability of fulvestrant and the steroidal AI, exemestane, in patients with locally advanced or metastatic breast cancer who have progressed or recurred while receiving a non-steroidal AI. EFECT confirmed that fulvestrant and exemestane offer effective treatment options in this setting. Similar efficacy was seen in both treatment groups and there were no significant differences in reported adverse events between fulvestrant and exemestane. The EFECT data provide further evidence for the activity of fulvestrant in the treatment of advanced breast cancer. Other ongoing fulvestrant trials will further define its full role, including the potential for a high-dose regimen, combination of fulvestrant with an AI, and identification of clinical and biological markers to help in targeting those patients who are most likely to respond to treatment.     

Endocrine therapy for hormone treatment-naïve advanced breast cancer

A proportion of patients with hormone receptor-positive locally advanced or metastatic breast cancer will not have received prior endocrine therapy. However, there are limited clinical data specifically in these patients. We conducted a review of randomized phase II and III clinical studies of anastrozole, letrozole, exemestane, palbociclib, and fulvestrant to determine the evidence base supporting use of specific endocrine therapies in this patient population. From our findings, there is a paucity of clinical studies in patients with endocrine therapy-naïve disease; however, it appears that first-line treatment effects are consistent between patients who have and have not received prior endocrine treatment.     

The apoptotic action of estrogen following exhaustive antihormonal therapy: a new clinical treatment strategy

Long-term antihormonal therapy is effective at controlling the recurrence of estrogen receptor (ER)-positive breast cancer, but there may be unanticipated consequences for the development of new forms of drug resistance. Laboratory studies of exhaustive antihormonal therapy demonstrate there are at least two phases of resistance to selective ER modulators (SERMs; tamoxifen and raloxifene) and to estrogen withdrawal (aromatase inhibitors). In Phase I drug resistance, estrogen or a SERM promote tumor growth, but in Phase II drug resistance estrogen induces apoptosis. Understanding of the new biology of estrogen action has clinical relevance. There are paradoxical interactions between fulvestrant and postmenopausal levels of estrogen that cause robust growth of Phase II tamoxifen resistance or autonomous aromatase-resistant tumors. These new data suggest a rational approach for the treatment of patients with ER-positive breast cancer that have failed exhaustive antihormonal treatment. Low-dose estrogen could be used to debulk patients followed by fulvestrant in a low estrogen environment (aromatase treatment) to maintain tumor control.     

Surviving metastatic breast cancer for 18 years: a case report and review of the literature

We report a case of a 93-year-old woman who was diagnosed with estrogen receptor (ER)-positive, progesterone receptor-positive, T2N0M0 (stage I) breast cancer (BC) at the age of 45. Twenty-two years later, she was diagnosed with metastatic lesions to the lungs consistent with the breast primary. Her disease was stable on tamoxifen, anastrozole, and exemestane for 14 years. Subsequently, she was found to have metastatic lesions to thoracic spine as well as progressively increasing bilateral pleural effusions. At that time, she was deemed not to be a good candidate for chemotherapy and therapy was changed to fulvestrant. Two years later (38 years after initial diagnosis of BC), she was diagnosed with new metastatic liver lesions; although her pulmonary and bone metastases remained stable. Therefore, she was started on palliative chemotherapy with single-agent capecitabine. The treatment was discontinued after the second cycle upon the patient's request owing to grade 2 hand and foot syndrome. She expired 2 years later after fighting BC for four decades. She survived for 18 years after the diagnosis of metastatic breast cancer (MBC) while maintaining a good quality of life. To the authors' knowledge, this is the first reported case in the literature with the longest overall survival in a patient with MBC. We provide a detailed clinical analysis in conjunction with a brief literature review.     

Pathologic changes in breast cancer after anti-estrogen therapy

Breast cancer patients do not commonly receive anti-estrogens prior to surgical excision. We reviewed a cohort of patients who received preoperative anti-estrogen therapy after baseline biopsy and then had a repeat biopsy after several weeks on treatment. Patients with estrogen receptor positive tumors received anastrozole and fulvestrant in combination with gefitinib. Core needle biopsies were performed at day 1 and 21, and tumors were completely excised if operable at day 112. All patients were postmenopausal. Following treatment, tumors had degenerative changes including smudged nuclei, decreased nuclear size, intranuclear vacuoles, vacuolated cytoplasm, and increased cellular discohesion. In addition, increased tubule formation and intracytoplasmic lumina were seen in 6/9 cases (66.7%) and decreased mitotic rate was demonstrated in 7/9 cases (77.8%). These findings indicate increased differentiation of the tumor cells in response to anti-estrogen therapy and that may correlate with clinical response.     

New findings about endocrine therapy for breast cancer

For over a decade, the selective estrogen receptor modulator, tamoxifen, has been the primary agent for adjuvant endocrine therapy for steroid receptor-positive breast cancer. New data over the last 2 years now suggest that its primacy may be challenged by strategies that lower circulating and/or intratumoral estrogens. Recent trials support the use of ovarian suppression approaches with or without tamoxifen in place of chemotherapy in premenopausal women. A large randomized trial has also established the short-term efficacy and safety of the aromatase inhibitor, anastrozole, in postmenopausal women. How and when to integrate these new approaches into standard practice are topics of debate. Ongoing research is focused on choice of endocrine approach, duration and sequencing of endocrine treatment, identification of better predictive markers for hormone response, and assessment of long-term risks and benefits.     

Quantitative Progesterone Receptor Expression and Efficacy of Anti‐estrogen Therapy in Breast Cancer

The central role of estrogen receptor (ER) presence in predicting which breast cancer patients are likely to benefit from anti‐estrogen therapies is well‐established, but the added benefit of progesterone receptor (PR) and in particular low levels of PR is less well understood. The objective of this study was to determine the quantitative relationship between borderline levels of PR and subsequent benefit from anti‐estrogen therapy. We examined data from 447 patients, age 50 or older. ER and PR levels were quantitated by conventional ligand binding assay and Scatchard plot analysis or by enzyme‐linked immunoassay. Comparison of clinical outcome in relation with ER and PR status was calculated using Kaplan‐Meier actuarial survival analysis and the log‐rank test. Subpopulation treatment effect pattern plot (STEPP) analysis was used to explore the interaction between treatment effects and ER or PR levels for the 409 patients with ER values greater than 0. For anti‐estrogen treated patients, when the ER and PR positivity cut‐off was set at 1.0 fmole/mg protein, there was a statistically significant advantage for patients with ER+PR+ over ER+ PR? tumors for both breast cancer‐free interval (BCFI) and overall survival (OS). STEPP analysis found no overall interaction between treatment outcome (5 year survival probability) and levels of hormone receptor. However, patients with borderline PR levels did not appear to benefit from anti‐estrogen therapy. PR levels above borderline in addition to the presence of ER predicts an increased probability of benefit from anti‐estrogen therapy in breast cancer patients.     

“The emerging role of capivasertib in breast cancer”

Over 50% of breast tumors harbor alterations in one or more genes of the phosphatidylinositol 3-kinase (PI3K) pathway including PIK3CA mutations (31%), PTEN loss (34%), PTEN mutations (5%) and AKT1 mutations (3%). While PI3K and mTOR inhibitors are already approved in advanced breast cancer, AKT inhibitors have been recently developed as a new therapeutic approach. Capivasertib (AZD5363) is a novel, selective ATP-competitive pan-AKT kinase inhibitor that exerts similar activity against the three AKT isoforms, AKT1, AKT2, and AKT3. Preclinical studies demonstrated efficacy of capivasertib in breast cancer cell lines as a single agent or in combination with anti-HER2 agents and endocrine treatment, especially in tumors with PIK3CA or MTOR alterations. Phase I/II studies demonstrated greater efficacy when capivasertib was co-administered with paclitaxel, fulvestrant in hormone receptor (HR)-positive, HER2-negative breast cancer or olaparib. The recommended phase II dose of capivasertib as monotherapy was 480 mg bid on a 4-days-on, 3-days-off dosing schedule. Toxicity profile proved to be manageable with hyperglycemia (20–24%), diarrhea (14–17%) and maculopapular rash (11–16%) being the most common grade ≥3 adverse events. Ongoing Phase III trials of capivasertib in combination with fulvestrant (CAPItello-291), CDK4/6 inhibitor palbociclib (CAPItello-292) and paclitaxel (CAPItello- 290) will better clarify the therapeutic role of capivasertib in breast cancer.     

Evaluation of endometrial thickness in hormone receptor positive early stage breast cancer postmenopausal women switching from adjuvant tamoxifen treatment to anastrozole

Evaluation of endometrial thickness by transvaginal ultrasonography (TVUS) in postmenopausal estrogen receptor positive breast cancer patients treated with anastrozole after tamoxifen therapy. This study included 70 postmenopausal estrogen receptor positive breast cancer patients who switched to anastrozole after tamoxifen; patients had endometrial thickness >4 mm and no endometrial malignancy. Endometrial thickness was measured after anastrozole treatment. Endometrial thickness during anastrozole therapy was lower than after tamoxifen therapy (p < 0.001); the mean reduction in endometrial thickness was 4.5 mm (±3.0). Cystic endometrial appearance was more frequent in patients under tamoxifen than in those under anastrozole (p < 0.001). Duration of tamoxifen therapy was not correlated to the endometrial thickness at the time of its suspension. Duration of tamoxifen therapy and endometrial thickness at the time of tamoxifen suspension was correlated to the relative reduction of endometrial thickness during anastrozole therapy. Anastrozole reverses tamoxifen-induced increased endometrial thickness and sonographic endometrial cystic appearance.     

First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study

ObjectivesThe double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post-hoc analysis investigated the efficacy and safety of fulvestrant given either first-line or second-line for advanced disease.Materials & methodsProgression-free survival (PFS) and overall survival (OS) with fulvestrant 500 mg vs fulvestrant 250 mg was evaluated using unadjusted log-rank tests in patients treated in the first- (progression during or within 12 months after completing adjuvant endocrine therapy; n = 387) and second-line (following endocrine therapy for LA/MBC; n = 343) settings.ResultsFirst-line fulvestrant 500 mg significantly prolonged PFS vs fulvestrant 250 mg (median PFS 5.6 vs 4.2 months; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.64–1.00; p = .047). Median PFS was numerically greater with second-line fulvestrant 500 mg vs fulvestrant 250 mg (7.9 vs 6.3 months; HR 0.80; 95% CI 0.64–1.02; p = .068). At data cut-off (75.5% maturity), median OS with first-line fulvestrant 500 mg was 23.2 vs 22.1 months with fulvestrant 250 mg (HR 0.87; 95% CI 0.70–1.10; p = .251), and 29.2 vs 22.8 months, respectively, in the second-line (HR 0.75; 95% CI 0.58–0.96; p = .020). The safety profile was broadly comparable between dose groups and across treatment lines, and consistent with the overall patient population.ConclusionThe superiority of fulvestrant 500 mg over fulvestrant 250 mg in patients with LA/MBC in CONFIRM was consistent in both the first- and second-line settings for PFS, and numerically greater in both settings for OS.     

Concordance of the hormone receptors and correlation of HER-2/neu overexpression of the metachronous cancers of contralateral breasts

The primary objective of this study was to evaluate the relative prevalence of estrogen receptor-negative contralateral breast cancer to the first primary cancer and to assess the correlation between the relative overexpression of HER-2/neu in the first primary cancer and contralateral breast cancer. A total of 144 women diagnosed with cancers in contralateral breasts were identified from the Henry Ford Health System tumor registry. Data were retrieved from electronic databases and medical records. Women were dichotomized into users and nonusers of tamoxifen. Hormone receptors were scored as positive or negative. HER-2/neu overexpression, assessed by immunohistochemistry, was scored as 0, 1(+), 2(+), or 3(+). Concordance between hormone receptors of the two cancers was low (kappa = 0.27, p = 0.06). Stratification of women by tamoxifen therapy yielded an almost fivefold increase in the proportion of estrogen receptor-negative cancers among the users, while the proportion of cancers expressing no estrogen receptor remained the same among the nonusers (39.6% versus 40.6%). Matched, archived, paraffin-embedded specimens of the first and contralateral breast cancers were available for 57 women. The correlation between the relative overexpression of HER-2/neu between the first primary and the contralateral breast cancer was 0.4 (p = 0.002). The higher prevalence of estrogen receptor-negative contralateral breast cancer among tamoxifen users concurs with previous reports. The biological mechanism for this observation is not understood; however, it has been proposed that tamoxifen inhibits the proliferation of estrogen receptor-positive breast cancer cells, while estrogen receptor-negative cells may continue to grow because of selective pressure. The correlation between HER-2/neu overexpression in the matched first primary and contralateral breast cancers was statistically significant, suggesting that the diagnosis of HER-2/neu overexpression in contralateral breast cancer is associated with HER-2/neu overexpression in the first primary cancer.     

Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant

HYPOTHESIS: Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)-positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells. DESIGN: Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S. SETTING: Surgical oncology research laboratory. INTERVENTIONS: The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 microg/dL (22.8 micromol/L) of DHEA-S. MAIN OUTCOME MEASURES: Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thiazolyl blue, were performed on the third, fifth, and seventh days poststimulation and permitted the calculation of growth percent change. RESULTS: The ER-positive and progesterone receptor-positive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptor-negative cells demonstrated growth inhibition. CONCLUSIONS: The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.     

Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer

The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease.The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy.However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research.This review focuses on current and emerging treatments for HR+ metastatic breast cancer.     

Understanding the benefits and challenges of first‐line cyclin‐dependent kinases 4 and 6 inhibitors in advanced breast cancer among postmenopausal women

Endocrine therapy (ET) has been regarded for many years as the standard treatment for patients with hormone receptor‐positive (ER+), HER2‐negative (HER2?) advanced breast cancer (ABC) without visceral crisis. However, the efficacy of single‐agent ET is constrained by the development of resistance, attributed to alterations in several intracellular signaling pathways, including those related to cell cycle dysregulation. The cyclin‐dependent kinases 4 and 6 (CDK4/6) are principal regulators of cell cycle progression from the G1‐phase into the DNA synthesis (S)‐phase. In vitro inhibition of CDK4/6 activity has potent antiproliferative properties against luminal breast cancer cell lines, which are enhanced when combined with traditional ET. This has led to a substantial interest in targeting this pathway to overcome endocrine resistance in the clinic. Three selective CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) have been approved as first‐line therapy in combination with an aromatase inhibitor, or fulvestrant in the case of ribociclib in patients with ER+/HER2? ABC. To date, there is no clue as to which subgroup of patients might benefit most from these combinations. Here, we outline some of the established approaches to overcome endocrine resistance, with special emphasis on the unique mechanism of action of CDK4/6 inhibitors.     

Efficacy and safety of palbociclib plus endocrine therapy in North American women with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer

Palbociclib is a cyclin‐dependent kinase 4/6 inhibitor indicated for treatment of hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer in combination with endocrine therapy. We investigated the efficacy and safety of palbociclib in patients enrolled in North America during two‐phase 3 trials: PALOMA‐2 (n = 267, data cutoff: May 31, 2017) and PALOMA‐3 (n = 240, data cutoffs: April 13, 2018, for overall survival, October 23, 2015, for all other outcomes). In PALOMA‐2, treatment‐naïve postmenopausal patients with advanced breast cancer were randomized 2:1 to palbociclib (125 mg/d; 3 weeks on/1 week off [3/1]) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. In PALOMA‐3, patients who progressed on prior endocrine therapy were randomized 2:1 to palbociclib (125 mg/d; 3/1) plus fulvestrant (500 mg, per standard of care) or placebo plus fulvestrant; pre/perimenopausal patients received ovarian suppression with goserelin. Palbociclib plus endocrine therapy prolonged median progression‐free survival vs placebo plus endocrine therapy in North American patients (PALOMA‐2: 25.4 vs 13.7 months, hazard ratio, 0.54 [95% CI, 0.40–0.74], P < .0001; PALOMA‐3: 9.9 vs 3.5 months, hazard ratio, 0.52 [95% CI, 0.38–0.72], P < .0001). Objective response and clinical benefit response rates were greater with palbociclib vs placebo in North American patients in both trials. While overall survival data are not yet mature for PALOMA‐2, median overall survival was increased in PALOMA‐3 (32.0 vs 24.7 months, hazard ratio, 0.75 [95% CI, 0.53–1.04]), though this did not reach statistical significance (P = .0869). Safety profiles in North American patients were similar to those of the overall populations; neutropenia was the most common treatment‐emergent adverse event. No new safety signals were observed. In summary, palbociclib plus endocrine therapy is an effective treatment option for North American women with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.     

Real-World Efficacy of Fulvestrant Monotherapy as the First Treatment or Maintenance Treatment in Patients with Metastatic Breast Cancer

BackgroundFulvestrant 500 mg monotherapy is recommended as the first-line endocrine treatment in postmenopausal women with hormone receptor-positive metastatic breast cancer (MBC). It is also used in MBC maintenance treatment. However, few studies have compared the efficacy of fulvestrant during the initial treatment with that during maintenance treatment.Patients and MethodsMBC patients who were treated with fulvestrant either as initial therapy for metastatic disease or after progression following one line of chemotherapy between January 2016 and December 2017 were identified from the database of the Affiliated Hospital of Qingdao University. The primary end point was progression-free survival (PFS).ResultsThe study included 135 MBC patients who were treated with fulvestrant; 116 patients who received fulvestrant as first-line treatment were divided into 2 groups: the no-chemotherapy treatment (NCT) group received fulvestrant as initial therapy during disease progression, and the chemotherapy treatment (CT) group received fulvestrant as maintenance following disease stabilization or response to previous chemotherapy. The median PFS was 16 months in NCT patients and 8 months in the CT group. Patients who had a longer disease-free survival, no visceral metastasis and one metastasis site, benefited from fulvestrant as first-line treatment during disease progression. Patients with 2 or more metastasis sites benefited from chemotherapy as first-line treatment and fulvestrant as maintenance treatment.ConclusionsFulvestrant monotherapy showed good clinical activity and safety in patients with MBC who were treated upon disease progression and in those receiving maintenance therapy.