阿那曲唑联合放疗治疗老年早期乳腺癌的疗效评价

目的 探讨阿那曲唑联合放疗治疗老年早期乳腺癌的临床疗效及对患者生存质量的影响.方法 回顾性分析98例老年女性乳腺癌保乳术后患者的临床资料,根据治疗方法不同将患者分为观察组(n=45)和对照组(n=53).观察组予以阿那曲唑联合放疗治疗,对照组予以常规阿那曲唑内分泌治疗.观察两组患者的5年累积生存率、复发率及生存质量.结果 观察组和对照组的5年累积生存率分别为80.0%和64.2%,差异有统计学意义(P﹤0.05);观察组患者术后5年的复发率为24.4%(11/45),低于对照组的45.3%(24/53),差异有统计学意义(P﹤0.05).治疗后3个月观察组患者的生存质量明显低于对照组(P﹤0.01),但治疗后6个月和12个月两组患者生存质量比较,差异无统计学意义(P﹥0.05).结论 阿那曲唑联合放疗治疗老年早期乳腺癌可提高患者生存率,降低复发率.     

Clinical and endocrine data for goserelin plus anastrozole as second-line endocrine therapy for premenopausal advanced breast cancer

A total of 16 premenopausal women with metastatic breast cancer (N=13) or locally advanced primary breast cancer (N=3) were treated with a combination of a gonadotropin-releasing hormone agonist goserelin, and a selective aromatase inhibitor anastrozole. All had previously been treated with goserelin and tamoxifen. In all, 12 patients (75%) achieved objective response or durable stable disease at 6 months, with a median duration of remission of 17+ months (range 6-47 months). Four patients still have clinical benefit. Introduction of goserelin and tamoxifen resulted in an 89% reduction in mean oestradiol levels (pretreatment vs 6 months=224 vs 24 pmol l(-1)) (P<0.0001). Substitution of tamoxifen by anastrozole on progression resulted in a further 76% fall (to 6 pmol l(-1) at 3 months) (P<0.0001). Treatment with goserelin and tamoxifen led to a 90% fall in the mean follicle-stimulating hormone (P<0.001). This was reversed once therapy was changed to goserelin and anastrozole. A similar initial reduction was seen in the mean luteinising hormone levels, but substitution of tamoxifen by anastrozole on progression resulted in no significant change. Goserelin and tamoxifen did not lead to any significant change in testosterone and androstenedione levels. The combined use of goserelin and anastrozole as second-line endocrine therapy produces a significant clinical response of worthwhile duration, with demonstrable endocrine changes, in premenopausal women with advanced breast cancer, and offers them another therapeutic option. Further studies involving more patients and longer follow-up are indicated.     

Review of the ATAC study: tamoxifen versus anastrozole in early-stage breast cancer

A 5-year regimen of tamoxifen hormone therapy has historically been the recommendation for hormone receptor-positive, postmenopausal women with early-stage breast cancer. With the advent of aromatase inhibitors, there has been extensive work carried out to investigate the role of these agents in the adjuvant setting. Studies have been designed to answer whether these agents should be used upfront (instead of tamoxifen) or in conjunction (either in a switch or extended program). The Arimidex^®, Tamoxifen Alone or in Combination (ATAC) trial is a landmark trial that demonstrated the superiority of upfront anastrozole over tamoxifen. This article reviews the trial and discusses both the optimum timing of initiation of aromatase inhibitors and the future approach of more individualized therapy, with the detection of predictive markers.     

Color doppler ultrasound as an objective assessment tool for chemotherapeutic response in advanced breast cancer

BACKGROUND: In our part of the world, the majority of the patients with breast cancer present with locally advanced disease and require neo-adjuvant chemotherapy as the primary treatment modality. It is essential to monitor the response to chemotherapy in these patients. Clinical examination as the sole criterion of response assessment is entirely subjective and fallacious. Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are expensive. The role of Doppler ultrasonography as an imaging modality for this purpose is therefore being evaluated. METHODS: A prospective study was undertaken of 25 cases of locally advanced breast carcinoma (LABC) and Color Doppler sonography was used for the sequential assessment of chemotherapeutic response. The response assessed on the basis of clinical examination and Color Doppler was compared with the histological response. The parameters assessed on color Doppler were a change in the number of flow signals, maximum flow velocity (Vmax), pulsatility index (PI) and resistivity index (RI). Responses were analysed statistically using the Pearson correlation coefficient and Kappa statistics (kappa). The sensitivity, specificity, positive predictive & negative predictive values for predicting complete histological response were calculated. RESULTS: Color Doppler showed a sensitivity of 88.88 % for predicting complete histological response. The negative predictive value of color Doppler was 92.3 %. A significant correlation was obtained between color Doppler and histopathological response. CONCLUSIONS: Color Doppler was found to be an objective and effective tool or modality compared with clinical evaluation in sequential response assessment, especially for predicting complete histological response.     

Analysis of Ki‐67 expression with neoadjuvant anastrozole or tamoxifen in patients receiving goserelin for premenopausal breast cancer

BACKGROUND:

The increasing costs associated with large‐scale adjuvant trials mean that the prognostic value of biologic markers is increasingly important. The expression of nuclear antigen Ki‐67, a marker of cell proliferation, has been correlated with treatment efficacy and is being investigated for its value as a predictive marker of therapeutic response. In the current study, the authors explored correlations between Ki‐67 expression and tumor response, estrogen receptor (ER) status, progesterone receptor (PgR) status, and histopathologic response from the STAGE study (S_ tudy of T_ amoxifen or A_ rimidex, combined with G_ oserelin acetate to compare E_ fficacy and safety).

METHODS:

In a phase 3, double‐blind, randomized trial (National Clinical Trials identifier NCT00605267), premenopausal women with ER‐positive, early stage breast cancer received either anastrozole plus goserelin or tamoxifen plus goserelin for 24 weeks before surgery. The Ki‐67 index, hormone receptor (ER and PgR) status, and histopathologic responses were determined from histopathologic samples that were obtained from core‐needle biopsies at baseline and at surgery. Tumor response was determined by using magnetic resonance imaging or computed tomography.

RESULTS:

In total, 197 patients were randomized to receive either anastrozole plus goserelin (n = 98) or tamoxifen plus goserelin (n = 99). The best overall tumor response was better for the anastrozole group compared with the tamoxifen group both among patients who had a baseline Ki‐67 index ≥20% and among those who had a baseline Ki‐67 index <20%. There was no apparent correlation between baseline ER status and the Ki‐67 index in either group. Positive PgR status was reduced from baseline to week 24 in the anastrozole group.

CONCLUSIONS:

In premenopausal women with ER‐positive breast cancer, anastrozole produced a greater best overall tumor response compared with tamoxifen regardless of the baseline Ki‐67 index. Cancer 2013. © 2012 American Cancer Society.     

IBIS II: a breast cancer prevention trial in postmenopausal women using the aromatase inhibitor anastrozole

Tamoxifen has been shown to reduce the incidence of estrogen receptor-positive breast cancer by approximately 50% in high-risk women. Similar results are seen for raloxifene, but it has a more favorable side-effect profile. Data on contralateral tumors from women in adjuvant trials treated with aromatase inhibitors suggest that new tumors can be reduced by another 50% with these drugs, suggesting a potential 75% reduction of estrogen receptor-positive tumors when used in a prophylactic manner. Side effects appear to be fewer with the aromatase inhibitors, with no excess of gynecologic (including endometrial cancer) or thromboembolic events, but an increase in fracture risk and joint symptoms does occur. IBIS II is a placebo-controlled prevention trial evaluating 5 years of the aromatase inhibitor anastrozole in high-risk postmenopausal women. The primary end point is breast cancer incidence, but major efforts are also being directed at minimizing any fracture risk.     

Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer

Background:

The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.

Methods:

One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.

Results:

A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 53.8% (95% CI=39.5–67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 50.0% (95% CI=35.8–64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3–21.0) before, 3.2% (95% CI=1.9–5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1–22.5) before, 3.2% (95% CI=1.8–5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.

Conclusions:

Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.     

A case report of advanced male breast cancer with an objective response to tamoxifen treatment

A 70-year-old man presented with a firm tumor in his right breast first noticed eight years ago.The tumor had enlarged gradually and had produced an ulcer with bleeding. On physical examination, a huge tumor entirely occupied the right breast and extensively had infiltrated the chest wall.Chest X-ray and CT showed massive pleural effusion and multiple small nodular lesions in the lung. Invasive ductal carcinoma of the breast was diagnosed by incisional biopsy,confirming advanced breast cancer with lung metastases and bilateral pleural effusion(T4cN2M1, Stage IV). Because ER and PgR levels were 110 fmol/mg and 190 fmol/mg, respectively, and because his general condition was poor, we selected medical treatment with tamoxifen(TAM). Thirty-two weeks later, the tumor had showed pronounced reduction with scarring. The patient underwent local excision of the scar tissue. The quality of life of the patient was favorably improved and no severe adverse events were observed. The tumor in the chest wall recurred two months after the end of TAM treatment, possibly because the patient did not accept continuous TAM therapy. The patient died from complications of brain metastasis 32 months after the start of TAM treatment. We report a rare case of advanced male breast cancer and on the effectiveness of continuous TAM treatment.     

Biological activity of anastrozole in postmenopausal patients with advanced breast cancer: effects on estrogens and bone metabolism.

BACKGROUND: To study the short-term biological effect of anastrozole on serum estrogens, androgens, 17-hydroxyprogesterone (17OH-PGR), gonadotrophins, sex hormone binding globulin (SHBG) and bone metabolism markers. MATERIALS AND METHODS: Thirty-four consecutive patients with advanced breast cancer received anastrozole 1 mg/day. Blood samples were taken before commencement of treatment and at 2, 4, 8 and 12 weeks during treatment to measure serum levels of estrogens (E(1), E(2) and E(1)-S), androgens [androstenedione (Delta(4)), dihydrotestosterone (DHT), testosterone (TST), free TST, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S)], 17OH-PGR, SHBG and gonadotrophins. As an indicator of bone resorption, we measured serum levels of C-terminal telopeptide of type I collagen (ICTP) and the cross-linked N-telopeptide of type I collagen (NTx), and for osteoblastic activity, intact osteocalcin (BGP) and bone alkaline phosphatase (BAP). RESULTS: After 2 weeks E(1 )and E(1)-S levels decreased on average by 56% (range 23.1-88.8%) and 75.8% (range 52.4-87.2%), respectively; E(2) decreased on average by 62% (range 31.4-89.6%). No significant changes were detected in levels of androgens or 17OH-PGR. There was a significant increase in gonadotrophins over time (P = 0.0001 for both luteinizing hormone and follicle-stimulating hormone), and a significant decrease in SHBG (P = 0.0001). A progressive significant increase in bone metabolism serum markers was detected in all patients: BAP, P = 0.039; BGP, P = 0.016; ICTP, P = 0.0021; and NTx, P = 0.0013. In particular, patients with bone metastases had a statistically significant increase of bone resorption markers (ICTP, P = 0.0019; NTx, P = 0.025) and borderline for bone formation markers. In patients without bone disease, BAP, BGP and ICTP remained unchanged, whereas serum NTx significantly increased (P = 0.019). CONCLUSIONS: Anastrozole is a selective aromatase inhibitor as it does not modify serum levels of androgens and 17OH-PGR. In our experience no relationship was found in the short-term period between serum estrogen suppression and bone metabolism.     

Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted > or = 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.     

Exemestane versus anastrozole as front-line endocrine therapy in postmenopausal patients with hormone receptor-positive, advanced breast cancer: final results from the Spanish Breast Cancer Group 2001-03 phase 2 randomized trial

BACKGROUND:

Several aromatase inhibitor studies have reported variations in the inhibitory potency of these agents that could lead to differences in clinical outcomes. In the current study, the authors formally evaluated the activity of anastrozole and exemestane in postmenopausal women with hormone‐responsive, advanced breast cancer.

METHODS:

Postmenopausal women who had measurable disease according to Response Evaluation Criteria in Solid Tumors and had not received previous endocrine therapy for advanced breast cancer were randomized to receive either oral exemestane 25 mg daily or oral anastrozole 1 mg daily until they had disease progression. The primary endpoint was the objective response rate (ORR), and secondary endpoints included the clinical benefit rate (CBR), time to progression (TTP), overall survival, and safety. Crossover to the other aromatase inhibitor was permitted at the time of disease progression; ORR, CBR, and TTP after second‐line treatment also were explored.

RESULTS:

In total, 103 patients were enrolled. The median patient age was 71.6 years, 52.4% of patients had visceral disease, and 75.8% of patients had ≥2 disease sites. Half of the patients had received previous tamoxifen, and 60% had received previous chemotherapy. The efficacy observed in the exemestane and anastrozole groups was an ORR of 36.2% and 46%, respectively; a CBR of 59.6% and 68%, respectively, and a TTP of 6.1 months and 12.1 months, respectively. At progression, 28 patients crossed over to the other aromatase inhibitor, including 16 patients who switched to exemestane (CBR, 43.7%; TTP, 4.4 months) and 12 patients who switched to anastrozole (CBR, 8.3%; TTP, 2 months). Both drugs were generally well tolerated, and no study drug‐related serious adverse events were reported.

CONCLUSIONS:

In this phase 2 randomized trial, no significant differences in clinical activity were observed in favor of exemestane to justify a superiority phase 3 trial design in the first‐line setting. Cancer 2012;. © 2011 American Cancer Society.     

Efficacy of adjuvant aromatase inhibitor in hormone receptor-positive postmenopausal breast cancer patients according to the body mass index

Background:

Increased adiposity may trigger signalling pathways that induce aromatase expression. As aromatase inhibitors exert their effects by blocking the aromatase enzyme, higher body mass index (BMI) can reduce the effect of aromatase inhibitors. Thus, we aimed to investigate retrospectively the effect of BMI on the efficacy of aromatase inhibitors in hormone receptor-positive postmenopausal patients with breast cancer.

Methods:

Newly diagnosed hormone receptor-positive breast cancer patients who were postmenopausal and non-metastatic were enrolled to the study. Patients with BMI ranging between 18.5 and 24.9 kg m⁻² were considered as normal weight patients (Arm A, n=102), and patients with a BMI ranging ⩾25 kg m⁻² were grouped as overweight and obese patients (Arm B, n=399).

Results:

In both normal weight and overweight patients, the baseline clinico-pathologic properties and the treatment history with radiotherapy and chemotherapy were similar, and with no statistically significant difference. In normal weight patients disease-free survival (DFS) rate was 93.7% and 77.6%, whereas in overweight and obese patients DFS rate was 96.8% and 85.5% in the first and third years, respectively, (P=0.08). Three year survival rate in Arm A patients was 98.3%, whereas in Arm B was 98.0% (P=0.57). When anastrozole was compared with letrozole in the subgroup analysis no difference with regard to DFS and overall survival was detected.

Conclusion:

These results, contradictory to the prior results, show that BMI has no worse effect on outcomes of aromatase inhibitors in postmenopausal hormone receptor-positive breast cancer patients. In the subgroup analysis, letrozole and anastrozole had similar survival outcomes.     

Influence of non-measurable disease on progression-free survival in patients with metastatic breast cancer

BackgroundThe presence of non-measurable disease is common in metastatic breast cancer. It is unknown whether treatment effect on progression free survival (PFS) is consistent among patients with measurable and non-measurable disease.MethodsA systematic literature search identified phase III randomized controlled trials (RCTs) in metastatic breast cancer that reported outcomes in patients with non-measurable and measurable disease. Hazard ratios (HRs) and 95% confidence intervals were computed to compare the individual trial treatment effect on PFS in non-measurable versus measurable disease. Analyses were repeated for bone-only compared to non-bone-only disease and based on drug mechanism of action.ResultsAmong 82 RCTs that enrolled patients with non-measurable disease, data were available from 16 trials comprising 8516 patients. Treatment effect on PFS was similar in patients with non-measurable and measurable disease (HR for intra-study comparison = 1.01, p = 0.82). However, compared to non-bone-only disease, a significantly greater effect on PFS was seen in those with bone-only disease (HR 0.83, p = 0.03). Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, p = 0.01) and a lesser effect on PFS in RCTs of antiangiogenic drugs (HR 1.34, p = 0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy (HR 1.13, p = 0.23) and chemotherapy (HR 0.73, p = 0.22).ConclusionsThere is variability in treatment effect on PFS in patients with measurable and non-measurable disease, especially those with bone-only disease. Standardization of PFS determination in these patients is warranted.     

Impact of NHS breast screening on advanced disease and mortality from breast cancer in the North West of England

A cohort study was undertaken to describe outcomes from breast cancer in women who were aged 54 years or younger when they were first invited for NHS breast screening. The analysis included 5125 women invited for multiple rounds of breast screening by the Wigan screening programme and 10 750 women invited by the Manchester programme. The main outcome measures were rates of advanced disease and mortality from breast cancer. In Wigan 4028 (78.6%) and in Manchester 5485 (51.0%) women accepted all of their invitations for screening. The incidence of invasive cancer was higher in Wigan than in Manchester (24.78 vs 21.11 per 10 000 person-years; chi(2)=2.11, 1 df, P=0.15), but the rate of advanced disease was significantly lower (2.49 vs 4.73 per 10 000 person-years; chi(2)=4.36, 1 df, P=0.04). Mortality was lower in Wigan than in Manchester (2.46 vs 4.31 per 10 000 person-years; chi(2)=3.25, 1 df, P=0.07). In the first report of long-term outcomes in women invited for NHS breast screening, we demonstrated that it is possible to evaluate the impact of screening by comparing programmes with different proportions of regular attenders; a significant difference was shown in the rate of advanced disease between two programmes with different cancer detection and attendance rates.     

A prospective,randomized study on hepatotoxicity of anastrozole compared with tamoxifen in women with breast cancer

Tamoxifen and anastrozole are widely used as adjuvant treatment for early stage breast cancer, but their hepatotoxicity is not fully defined. We aimed to compare hepatotoxicity of anastrozole with tamoxifen in the adjuvant setting in postmenopausal breast cancer patients. Three hundred and fifty‐three Chinese postmenopausal women with hormone receptor‐positive early breast cancer were randomized to anastrozole or tamoxifen after optimal primary therapy. The primary end‐point was fatty liver disease, defined as a liver–spleen ratio <0.9 as determined using a computed tomography scan. The secondary end‐points included abnormal liver function and treatment failure during the 3‐year follow up. The cumulative incidence of fatty liver disease after 3 years was lower in the anastrozole arm than that of tamoxifen (14.6% vs 41.1%, P < 0.0001; relative risk, 0.30; 95% CI, 0.21–0.45). However, there was no difference in the cumulative incidence of abnormal liver function (24.6% vs 24.7%, P = 0.61). Interestingly, a higher treatment failure rate was observed in the tamoxifen arm compared with anastrozole and median times to treatment failure were 15.1 months and 37.1 months, respectively (P < 0.0001; HR, 0.27; 95% CI, 0.20–0.37). The most commonly reported adverse events were ‘reproductive system disorders’ in the tamoxifen group (17.1%), and ‘musculoskeletal disorders’ in the anastrozole group (14.6%). Postmenopausal women with hormone receptor‐positive breast cancer receiving adjuvant anastrozole displayed less fatty liver disease, suggesting that this drug had a more favorable hepatic safety profile than tamoxifen and may be preferred for patients with potential hepatic dysfunction.     

Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer.

BACKGROUND: In recent years, several cases of mandibular necrosis associated with long-term use of bisphosphonates have been reported. The estimated incidence varies from 1% to 4.6%. PATIENTS AND METHODS: We conducted an observational study with the aim of determining the incidence of jaw osteonecrosis in advanced breast cancer patients with bone metastases under bisphosphonate treatment and to identify subjects at higher risk of developing this complication evaluating preclinical signs. We considered two groups of patients. All the patients complaining of odontostomatological symptoms underwent maxillary CT scan and maxillo-surgeon clinical examination. Asymptomatic patients were asked to perform a standard orthopantomography (OPT). RESULTS: From February 2005 to October 2005, we observed five patients with jaw bone necrosis (6%). Diagnosis was radiological and clinical. In two patients a confirmatory biopsy was performed. In the same time interval, OPTs were collected from 76 asymptomatic patients. Three OPTs revealed radiological features of suspicious mandibular necrosis. Maxillary CT scan confirmed the presence of an osteolityc area with signs of periosteal reaction. All the three patients were referred to maxillo-surgeon and two out of three patients underwent mandibular biopsy, but histopathological results were not conclusive. CONCLUSIONS: In our experience, the incidence of jaw bone necrosis in breast cancer patients seems to be higher than in other reports (6%). Radiological features of suspicious jaw necrosis were observed in three asymptomatic patients. We do not know how these findings should be considered. Anyway, standard OPT is a simple procedure, and may allow identification of periodontal conditions that in some way can predispose to the development of this uncommon event.     

Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.