Hormone-sensitive Patients Research Articles

Evaluation of Factors Related to Late Recurrence - Later than 10 Years after the Initial Treatment - in Primary Breast Cancer

Background: Breast cancer is associated with a relatively good prognosis. Prognostic factors examined to date are related to early recurrence while those related to late recurrence and their countermeasures remain unclear. Therefore, we examined the factors related to late recurrence. Patients and Methods: From January 1980 to August 2012, 4,774 patients who underwent primary treatment and estrogen (ER) and progesterone receptor (PgR) assessment were enrolled in this study. The patients were divided into two groups, those with a follow-up period <10 years and those without any recurrence at 10 years but who continued follow-up examinations. Recurrence occurred in 711 patients followed up for <10 years and in 51 patients for ≥10 years. Results: The overall 10-year cumulative disease-free survival rate was 79.5%, and the recurrence rate at ≥10 years was 5.8%. A multivariate analysis revealed that the factors related to late recurrence were PgR positivity and positive nodes. This result differed from that for early recurrence in terms of ER/PgR, Ki-67 index and p53 overexpression. Conclusion: PgR positivity and lymph node metastases significantly correlated with late recurrence. Therefore, it is important to evaluate appropriate measures such as treatment period and treatment regimen for hormone-sensitive patients.

The relationship between tumor markers and histopathologic and demographic features of patients with breast cancer and their distinctive role in metastatic process.

e11540 Background: Tumor marker monitoring is generally performed by the physicians, although in many guidelines, it has not been recommended for breast cancer. In this study, we aimed to research the role of CEA and CA15.3 levels in metastatic process. Methods: In between years 2000 January and 2011 August, the documents of 482 female patients followed by breast cancer diagnosis in Medical Oncology and Radiation Oncology clinics of Kartal Dr. Lutfu Kirdar Education and Research Hospital, were evaluated retrospectively. Results: To determine the role of CEA and CA15.3 levels in evaluation of metastatic process, ROC analysis was performed and its cut-off values were 1.3 ng/ml and 14 U/ml, respectively. Sensitivities of CA15.3 and CEA levels were detected as 83.33% and 87.50%; specificities were 40.80% and 41.14%, respectively. Evaluation of the relationship between CEA and CA15.3 levels and the status of hormone receptors by ROC analysis showed the cut-off values as 26 U/ml and 1,6 ng/ml, respectively. In determination of endocrine sensitivity, the sensitivities of tumor markers elevation were 88.17% and 54.12%, respectively. Their specificities were 26.92% and 73.08%. CEA level elevation in hormone sensitive patients was statistically significant (p: 0.007). When sensitivity and specificity of CA15.3 and CEA levels on detection of c-erbB2 positivity were evaluated by ROC analysis, cut-off values were determined as 17 U/ml and 1,7 ng/ml. Sensitivities of these distinctive cut-off values were found as 58.8% and 71.15% and specificities were 60% and 51.67% (p: 0.017). When the relation between CA15.3 and CEA levels and node involvement was evaluated by ROC analysis, cut-off values were respectively 16 U/ml and 0.9 ng/ml. Their sensitivities were 53.45% and 87.93% and specificities were 55.56% and 51.67%, respectively. Conclusions: The levels of tumor markers have been suggested to have a significant role in prognosis of the disease with respecttothe correlation between different histopathological and clinical features and tumor markers. Randomised controlled prospective studies planned and performed in this issue may clarify this uncertainity.

Evaluation of factors related to late recurrence (later than 10 years after the primary treatment) in early breast cancer.

e11557 Background: Breast cancer is associated with a relatively good prognosis and heterogeneity. Prognostic factors examined to date are related to early recurrence while those related to late recurrence and their countermeasures remain unclear. Therefore, we examined the factors related to late recurrence, later than 10 years after primary treatment, in early breast cancer. Methods: From 1980 to August 2012, 4774 patients who underwent primary treatment, including operation and estrogen and progesterone receptors (ER and PgR) measurement, were enrolled in this study. The patients were divided into two groups, those with a follow-up period within 10 years, and those (1323 patients) without any recurrence at 10 years but who continued follow-up examinations. Recurrence occurred in 711 patients within 10 years and occurred in 51 patients from ≥10 years. The items examined were tumor size, lymph node status, and biological markers such as ER, PgR, Ki-67 values, p53 and human epidermal growth factor receptor 2 (HER2) expressions. Results: The overall 10-year cumulative disease-free survival (DFS) rate was 79.5%, and the recurrence rate at ≥10 years was 5.8% (some cases had recurrence 20 years later). A multivariate analysis revealed that the factors related to late recurrence were positive nodes and PgR positive. This result differed from that for early recurrence, where the DFS rate was low in patients with ER/PgR negative, high Ki-67 index values and p53 overexpression. Conclusions: The PgR positivity and lymph node metastasis significantly correlated with late recurrence (later than 10 years after primary treatment) in early breast cancer. Therefore, it is important to evaluate appropriate measures such as treatment period and treatment regimen for hormone-sensitive (ER and/or PgR positive) patients. In addition, how to inform patients about the recurrence rate and recurrence time from the initial treatment, and the Informed Consent regarding the follow-up period and surveillance plan must be examined.

P5-14-03: Genomic Comparison of Paired Primary Breast Carcinomas and Macrometastatic Lymph Node Metastases Using Quantitative RT-PCR by Oncotype DX: Assessment of the Recurrence Score and Quantitative Single Genes.

Abstract Background NCCN guidelines now include consideration of the 21 gene RT-PCR assay in node negative, hormone sensitive breast cancers greater than 0.6 cm. Recent data suggests a potential role for testing of node positive(N1), hormone sensitive patients as well. Currently, no data exists on testing of metastatic lymph nodes. We sought to establish the feasibility of Oncotype DX® testing in the metastatic lymph nodes and, furthermore, to evaluate the genomic concordance between the primary tumor and the nodal deposit. These results may further our understanding of tumor heterogeneity and biological selectivity in the process of lymph node metastasis and ultimately systemic metastases. Methods: We examined the formalin fixed paraffin embedded tumor tissues (FPET) from 100 breast cancer patients from our institution's pathology database with available paired primary tumor and macrometastic nodal deposits by Oncotype Dx® testing. Inclusion criteria included patients with macrometastatic lymph node disease, hormone receptor positive, HER2 negative primary breast cancer. The testing laboratory was blinded from the clinical outcomes data available on these patients. All FPET samples had H&amp;E slides made which were reviewed by board certified surgical breast pathologists to determine if there was sufficient invasive tumor and to direct dissection of all lymph node samples. The Recurrence Scores and quantitative single gene values from the paired samples will be examined descriptively with scatterplots and Pearson correlation coefficients and reported at the meeting. Results: All 100 paired specimens were sent for Oncotype DX testing. 24 samples were found during standard H&amp;E review to not have sufficient tumor for the assay. Of the 176 samples created for RNA extraction 173 samples had sufficient RNA for the Oncotype DX assay: 85 lymph node and 88 primary breast carcinoma samples. Recurrence Scores and quantitative single gene values from the paired primary breast carcinoma and lymph node samples will be examined descriptively and reported at the meeting. Conclusion: Previous comparisons of paired primary and metastatic samples have used immunohistochemistry and FISH which are susceptible to variability in preanalytic variability such as delay to fixation, choice of fixative and duration in fixative. This study, using quantitative RT-PCR, will be one of the largest comparisons of tumor biology in paired samples yet reported in the era of genomic subtyping and may have implications for systemic adjuvant treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-03.

Current role and safety profile of aromatase inhibitors in early breast cancer

The current adjuvant therapy for breast cancer is in a continous progress; standard therapeutic strategies include the use of chemotherapy, molecular targeted drugs and hormonal agents, according to well-established prognostic and predictive factors. Among the hormonal drugs, for a long period tamoxifen has been the gold standard of adjuvant therapy in postmenopausal women with hormone receptor-positive (HR+) early breast cancer. In the last years an expanding use of aromatase inhibitors occurred in this subset of patients, because the third-generation class of these agents (anastrozole, letrozole and exemestane) showed to be more effective and safe than tamoxifen and are now recommended as the preferred hormonal approach to postmenopausal hormone-sensitive patients, according to national and international guidelines. Treatment choices with these agents include the use of an aromatase inhibitor as an upfront strategy for 5 years, as a sequential approach after 2–3 years of tamoxifen, or as an extended use after the classical 5 years of tamoxifen. The improved efficacy of aromatase inhibitors over tamoxifen has been largely demonstrated in terms of better disease-free survival, reductions in the occurrence of early distant metastasis as well as improvement of overall survival. Moreover, according to the optimal duration of therapy, presently it is not known whether aromatase inhibitor therapy, as tamoxifen, should be limited to 5 years. In terms of safety profile, the side effects of aromatase inhibitors, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. There is strong evidence that aromatase inhibitors are well tolerated, with a lower incidence of gynecological symptoms (vaginal bleeding, discharge and endometrial neoplasia), venous thromboembolic events and hot flushes than tamoxifen. On the other hand, the use of aromatase inhibitors has been associated with loss of bone density, arthralgia, myalgia, and a negative effect on lipid metabolism and cardiovascular risk. More extensive and mature studies are necessary to well establish the safety of aromatase inhibitors when given to patients with breast cancer for a long time.

Abstract 3211: FGFR1 and FGFR2 gene copy number variations in prostate cancer

Abstract Patients with hormone refractory prostate cancer (HRPC) have very few clinical options. A bottle neck in development of new therapies is the poor understanding of the molecular basis of hormone independency. A pathway thought to be important in this progression is FGFR. Amplification of FGFR1 has been observed in breast cancer and has led to the hypothesis that it is involved in Tamoxifen resistance (Turner et al., 2010). Here we evaluated the copy number variations (CNV) of the gene loci of FGFR1 (8p12) and FGFR2 (10q26) by dual color FISH in FFPE tissue of recurrent PC patients (n=28), non-recurrent PC patients (n=15), PC patients undergoing palliative RPE (n=15), patients with benign prostate hyperplasia (n=17) and tumor free tissue samples (n=12). We analyzed CNV between different clinical patient subgroups. Two types of CNV for the gene loci of FGFR1 and FGFR2 were observed. Either the gene dose of the target gene locus occurred to be amplified or the gene dose was elevated due to polysomy of the respective chromosome. Furthermore patients with CNV of FGFR1 or FGFR2 exhibited in 40-50% intra tumor heterogeneity by presenting normal cells and cells with CNV. FGFR1 gene dose elevations (either due to gene locus amplification or polysomy of chromosome 8) were observed in 7% (1/15) of patients without recurrence but in 49% (17/35) of the patients with recurrence. Also, in patients undergoing palliative RPE 75% (12/16) of the patients exhibited FGFR1 gene dose elevation. In the case of FGFR2, gene dose elevations (gene locus amplification or polysomy of chromosome 10) were observed in none of the patients without recurrence but in 13% of the patients with recurrence and in 20% of patients undergoing palliative RPE. In the control groups such variations were not found. Interestingly, the gene dose variations differed in the prostate cancer patients depending on their hormone sensitivity. 47% (7/15) of hormone refractory patients and 30% (6/20) of the hormone sensitive patients showed elevated FGFR1 gene dose, for FGFR2, 30% and 20% of the respective subgroups were affected. In summary we conclude that this is first evidence that CNV of FGFR1 and FGFR2 might have implications for hormone resistance in PC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3211. doi:10.1158/1538-7445.AM2011-3211

Novel multi‐peptide vaccination in Hla‐A2+ hormone sensitive patients with biochemical relapse of prostate cancer

A phase I/II trial was conducted to assess feasibility and tolerability of tumor associated antigen peptide vaccination in hormone sensitive prostate carcinoma (PC) patients with biochemical recurrence after primary surgical treatment. Nineteen HLA-A2 positive patients with rising PSA without detectable metastatic disease or local recurrence received 11 HLA-A*0201-restricted and two HLA class II synthetic peptides derived from PC tumor antigens subcutaneously for 18 months or until PSA progression. The vaccine was emulgated in montanide ISA51 and combined with imiquimod, GM-CSF, mucin-1-mRNA/protamine complex, local hyperthermia or no adjuvant. PSA was assessed, geometric mean doubling times (DT) calculated and clinical performance monitored. PSA DT of 4 out of 19 patients (21%) increased from 4.9 to 25.8 months during vaccination. Out of these, two patients (11%) exhibited PSA stability for 28 and 31 months which were still continuing at data cut-off. One patient showed no change of PSA DT during vaccination but decline after the therapy. Three patients had an interim PSA decline or DT increase followed by DT decrease compared to baseline PSA DT. Three of the responding patients received imiquimod and one the mucin-1-mRNA/protamine complex as adjuvant; both are Toll-like receptor-7 agonists. Eleven (58%) patients had progressive PSA values. The vaccine was well tolerated, and no grade III or IV toxicity occurred. Multi-peptide vaccination stabilized or slowed down PSA progress in four of 19 cases. The vaccination approach is promising with moderate adverse events. Long-term stability delayed androgen deprivation up to 31 months. TLR-7 co-activation seems to be beneficial.

Efectividad y tolerabilidad del ácido zoledrónico en el tratamiento del cancer de próstata metastásico

ObjetivesTo assess the effectiveness and tolerability of zoledronic acid in prostate cancer patients with bone metastases at the hormone-sensitive (HS) and hormone-independent (HI) stages Materials and MethodsA nationwide, observational, prospective, open and multi-centre trial was devised, with a total of 218 male patients diagnosed with prostate cancer at the HS stage (36%) or HI stage (64%) who were administered zoledronic acid (4 mg/IV/month for 6 months) in addition to their specific oncological treatmentEffectiveness was assessed by the following means: 1) Assessment of the improvement in pain and mobility; 2) Incidence and time to onset of skeletal-related events (SREs) and 3) Analysis of bone markersTolerability was assessed by means of registering the number and type of adverse effects. A satisfaction survey was carried out amongst the patients after the end of the trial ResultsOut of the 218 patients, 170 (78%) were evaluable for effectiveness. A decrease in pain ratings at rest and during movement was observed in all patients, whether in the HS or HI groups (p<0,0001). Improved mobility was observed likewise (p=0,005), as was quality of lifeThe global incidence of skeletal events was 11.2%, with a time to onset of SREs of 10.7 months. There were no significant differences observed between HS vs. HI patientsOsteolysis markers (N-telopeptide) decreased significantly with the treatment across both the HS and HI groupsFor safety reasons, 212 patients were evaluable (97.2%). The incidence of adverse drug reactions was 16% (34/212) and was found to be significantly higher in HS patients (22.4%) compared with HI patients (11.9%). Overall, the tolerability of zoledronic acid was good, with no significant morbidity in either group (HS and HI). 66% of the patients reported feeling satisfied or very satisfied ConclusionsZoledronic acid proved effective in the relief of pain, improving mobility and quality of life as well as reducing or delaying the occurrence of skeletal-related events in prostate cancer patients presenting metastatic bone disease, regardless of the phase, whether HS or HI, they found themselves in. Tolerability and patient satisfaction were rates as good

Use of nuclear androgen receptor status to predict early biochemical recurrence of prostate cancer patients

21073 Background: Prostate cancer (PCa) is a leading cause of cancer death in North American men. The androgen receptor (AR) has an established role in the progression of this disease; however, it is unclear at what stage it intervenes. It is also uncertain whether the AR can be a useful prognostic marker for PCa. In this study, we assessed AR expression and sub-cellular localization in normal prostate as well as in androgen sensitive and insensitive PCa (AIPCa) tissues, and evaluated the ability of the AR to predict biochemical recurrence (BCR). Methods: We used tissue micro-arrays containing prostate tissue cores obtained from cancer-free patients (n=43), AIPCa patients (n=36), and patients with hormone-sensitive cancers (n=64) from which were collected both cancerous and normal adjacent tissue. Using immmunohistochemistry, we stained the tissue micro-arrays with a monoclonal antibody recognizing the AR. Two observers assessed the frequency and intensity of both cytoplasmic and nuclear AR staining. AR cytoplasmic (Ci) and nuclear (Ni) indices were calculated by multiplying nuclear staining frequency and nuclear staining intensity. Kaplan Meier, and Cox multivariate analyses were done using SPSS. Results: We found that AR Ci increased significantly in AIPCa although a modest but significant increase in PCa Ci was observed compared to normal tissues. In contrast, AR Ni was significantly lower in cancer-free patients as opposed to that seen in normal tissue adjacent to cancer. Similarly, cancerous tissue exhibited higher AR Ni than its adjacent normal tissue (p&lt;0.05, Kruskal-Wallis). Kaplan Meier analyses revealed that low AR Ni was predictive of an early onset of BCR (before 3-years) in the sub-cohort of hormone-sensitive patients (LR=6.51, p=0.011). Futhermore, low AR Ni remained an independent predictor of early BCR in a Cox multivariate model controlling for age, pre-operative PSA, lymph node invasion, Gleason score and surgical margin status (HR=2.28, 95% CI=1.04 - 5, p&lt;0.05). Conclusions: We conclude that increased nuclear AR activity could be a pre-malignant step in PCa progression whereas its role within cancer cells may be more complex, as low AR nuclear activity was associated with early onset of BCR. No significant financial relationships to disclose.

Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial

Background: The purpose of this study was to determine optimal adjuvant therapy between complete hormonal blockade in premenopausal patients with hormone receptor positive breast cancer and one to three positive nodes.Patients and methods: We randomised 333 patients to receive either LHRH agonist (triptorelin 3.75 mg i.m., monthly) plus tamoxifen 30 mg/day for 3 years (TAM-LHRHa, n = 164), or fluorouracil 500 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for six cycles, without any hormonal treatment (FEC50, n = 169).Results: The 7-year disease-free survival (DFS) was 76% with TAM-LHRHa, and 72% with FEC50 (P = 0.13). The 7-year overall survival (OS) was 91% and 88%, respectively (P = 0.20). The multivariate analysis confirmed that both treatments were not different for DFS and OS (P = 0.83 and P = 0.41, respectively). Amenorrhoea occurred in 64% of patients treated with FEC50; it was temporary in 58% of cases after hormonotherapy and in 31% after chemotherapy.Conclusion: In intermediate-risk breast cancer, complete hormonal blockade and chemotherapy provided similar outcomes. Hormonal treatment is an alternative to chemotherapy in hormone-sensitive patients, considering the preference of patients in terms of quality of life.

An elevated body mass (BMI) index predicts for better clinical outcomes in men with metastatic hormone refractory prostate cancer (HRPC)

4556 Background: Previous articles have reported that an elevated BMI was associated with an increased risk of biochemical failure in hormone sensitive patients. We asked the question as to whether an elevated BMI predicts for worst clinical outcomes, namely overall survival (OS) and prostate-cancer survival (PCS), among 1,216 men with HRPC. Methods: Patients were enrolled on eight clinical trials conducted by the Cancer and Leukemia Group B (CALGB). Eligible patients had progressive prostate cancer during androgen deprivation therapy (with documented castrate levels of testosterone), an ECOG performance status of 0–2, adequate hematologic, renal and hepatic function. We used the NIH definition to classify patients as: normal (&lt;25 kg/m2), overweight (25–29 kg/m2 ), mildly obese (30–34 kg/m2), and moderately to severely obese (≥35 kg/m2). PCS was defined as the time from study entry to the time of death due to prostate cancer. The proportional hazards model was used to explore the prognostic significance of BMI in predicting OS and PCS. Results: The median BMI was 27.7 kg/m2 (inter-quartile range = 25.2–31.0 kg/m2 ). Twenty three percent (285/1216) of the patients had normal BMI, 46% (555/1216) were overweight, 23% (280/1216) were mildly obese, and 8% (96/1216) were moderately to severely obese. In multivariate analysis, adjusting for age, race, performance status, hemoglobin, PSA, LDH, alkaline phosphatase, testosterone, years since diagnosis, presence of visceral disease and Gleason scores, BMI was a statistically significant predictor of OS and PCS. Compared to normal men, the hazard ratios (HR) of overweight patients was 0.80 (95% CI = 0.69–0.93, p-value = 0.003), for mildly obese patients was 0.86 (95% CI = 0.72–1.02, p-value = 0.087) and for moderately to severely obese men it was 0.60 (95% CI = 0.47–0.78, p-value &lt; 0.001). In addition, the HRs for PCS for overweight patients was 0.83 (95% CI = 0.70–0.97, p-value = 0.023), was 0.88 (95% CI = 0.72–1.06, p-value = 0.179) for mildly obese and for moderately to severely obese was 0.62 (95% CI = 0.47–0.81, p-value = 0.001) compared to men with normal BMI. Conclusions: Contrary to what was reported, these findings demonstrate an inverse relationship between BMI and clinical outcomes in men with HRPC. [Table: see text]

Gene profiling in transurethral resection samples of patients with hormone-refractory prostate cancer (HRPC)

4641 Background: Patients with metastatic carcinoma of the prostate (CaP) develop after a mean of 15 months resistance to hormone ablation therapy. However, the underlying molecular mechanisms are still unknown. Our goal was to identify the transcriptional changes that are characteristic for the transition to hormone resistant prostate cancer (HRPC) using oligonucleotide microarrays. Here, we report the attempt to profile fresh frozen tissue obtained by palliative transurethral resection (TUR) in patients with HRPC and concomittant urinary obstruction. Methods: Indications for palliative TUR were locally progressive tumors with obstruction and voiding problems. HRPC was defined according to the criteria of Scher et al. 1995. Samples of 8 HRPC patients were compared to tissues from 8 hormone-sensitive CaP patients including biological and technical replicates. All tissue samples had been pathologically evaluated. Only macrodissected prostate samples with at least 70% tumor content were used for RNA extraction. RNA quality was controlled using the Bioanalyzer Nanochip (Agilent Technologies, Palo Alto). Expression analysis was performed on Affymetrix oligonucleotide arrays. Results: We identified 323 genes being significantly deregulated (corrected p-value &lt;0.05, false discovery rate &lt;0.05). These genes were mapped to cellular pathways using the KEGG annotation and the most significantly deregulated pathways were identified. Deregulation of metabolic pathways included fatty acid metabolism as well as oxidative phosphorylation and ATP synthesis. Cell cycle control seems to be further suppressed by the downregulation of JNK-pathway via MEKK4 and JUND, the downregulation of p21 (CDKN1A) and the induction of Cylcin D1. We also present evidence for a significant downregulation of actin cyctoskeleton components. Deregulated genes likely to be specific for the transition from prostate carcinoma to HRPC will be presented. Conclusions: Gene expression profiling has been successfully standardised using fresh TUR material of HRPC patients. Deregulated genes have been mapped to specific signal transduction pathways. On this platform, clinical trials in patients with HRPC using specific inhibitors of cell signalling are being developed. [Table: see text]

Cost-effectiveness of letrozole in the treatment of advanced breast cancer

Aromatase inhibitors are fast becoming the treatment of choice in the first-line management of hormone-sensitive patients with metastatic breast cancer, replacing tamoxifen. Although these agents appear to have clinical superiority, they are more expensive alternatives, thus requiring economic evaluation to consider their incremental value to the payer. This article reviews all published economic evaluations that compared aromatase inhibitors in the first- and second-line treatment setting. From the literature, seven seperate evaluations were identified, which used different types of modeling techniques and considered the payer’s perspective in three healthcare systems. The conclusion of these analyses was that letrozole (Femara®, Novartis) is the most cost-effective intervention in the first-line setting, whilst being of similar cost-effectiveness to anastrozole (Arimidex®, AstraZeneca) in the second-line setting. In addition, preliminary results suggest that letrozole is a cost-effective alternative in the extended adjuvant breast cancer treatment setting.

Adjuvant Therapy for Early Breast Cancer in Pre-/Perimenopausal Women

The adjuvant treatment of pre- and perimenopausal breast cancer is an area of increasing importance as a result of the rising incidence of the disease and improvements in its detection and diagnosis. Recent years have seen a wider variety of treatments become available, presenting the possibility of increasingly individualized treatment regimens which provide benefits in terms of long-term survival and tolerability. Chemotherapy has been shown to provide a clear benefit to pre-/perimenopausal women with breast cancer, in particular the combination of cyclophosphamide, methotrexate, and fluorouracil (CMF), or more recently, anthracycline-containing regimens such as cyclophosphamide, doxorubicin, and fluorouracil (CAF). Trials examining the use of adjuvant taxanes have not shown a clear benefit so far compared with standard regimens. Adjuvant endocrine treatment has proved to be important in treating pre-/perimenopausal women with estrogen receptor positive tumors, providing clear evidence that treatment with tamoxifen for a period of 5 years is highly effective. Ovarian ablation has been shown to provide improvements in both overall and disease-free survival that are comparable to those provided by chemotherapy in hormone-sensitive patients whilst offering an improved tolerability profile compared with chemotherapy. Currently, evidence supporting the role of endocrine therapy combined with chemotherapy is limited. The increasing range of adjuvant treatment options available for pre-/perimenopausal breast cancer requires that patients be assessed individually to identify the most appropriate treatment option and that tolerability issues be discussed with the patient prior to the initiation of treatment.

CHANGES IN FREE AND FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN AFTER ANDROGEN DEPRIVATION OR CHEMOTHERAPY IN PATIENTS WITH ADVANCED PROSTATE CANCER

Purpose To provide preliminary data on whether the diagnostic role of serum prostate specific antigen (PSA) in assessing the response to treatment is improved by concomitant free PSA evaluation both markers were evaluated in 42 patients with advanced prostate cancer who received hormonal therapy and 57 with hormone refractory disease who received chemotherapy. Materials and Methods PSA was assessed at baseline and every 3 months during treatment. Free PSA was assessed in stored serum samples obtained at baseline and at maximum PSA decrease. Free PSA was not measurable in 17 patients who received androgen deprivation (40.5%) and 2 who received chemotherapy (3.5%) because it was less than 1.5 ng./ml. Results Of the 21 patients with greater than 50% PSA decrease after hormonal therapy free-to-total PSA increased in 12 (57.2%) and decreased in 9 (42.9%). Of the 20 patients with PSA response after chemotherapy free-to-total PSA increased in 18 (90.0%) and decreased in 2 (10.0%). Free-to-total PSA increased in 12 of the 20 patients (60.0%) with PSA stabilization after chemotherapy. Patients with an increase in free-to-total PSA after chemotherapy had greater survival compared to those with a decrease or no change (19.8 versus 15.5 months, respectively, p <0.03). Conclusions These data suggest that an effective cytotoxic regimen mainly affects the protein bound PSA fraction. The absence of a clear predominant pattern of free-to-total PSA in patients with PSA response to hormonal therapy and the high percentage of hormone sensitive patients in whom free PSA was not assessable at maximum PSA decrease suggest that free PSA evaluation is less useful in prostate cancer patients undergoing androgen deprivation.