Conservative surgery in stage I adult type granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). METHODS: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. RESULTS: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival. CONCLUSIONS: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach.

Duloxetine and escitalopram for hot flushes: efficacy and compliance in breast cancer survivors.

Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) might be an effective treatment for hot flushes (HFs) in breast cancer survivors (BCSs). This study aims to compare the efficacy and tolerability of duloxetine (SNRI) versus escitalopram (SSRI) in reducing frequency and severity of HFs in BCSs and to assess the effect on depression. Thirty-four symptomatic BCSs with emotional impairment received randomly duloxetine 60 mg daily or escitalopram 20 mg daily for 12 weeks. Patients were asked to record in a diary HF frequency and severity at baseline and after 4 and 12 weeks of treatment. Depression was evaluated through validated questionnaires (Beck Depression Inventory and Montgomery Asberg Depression Rating Scale) at baseline and after 4 and 12 weeks of treatment. Both drugs showed a significant reduction of HF frequency and severity after 12 weeks of treatment with no significant difference between the two groups. A significant improvement in depression symptoms was observed at the end of the study period within both the groups, without difference between the two drugs. In conclusion, escitalopram and duloxetine are both effective treatment for the relief of HFs in BCSs, with similar beneficial effect. A significant improvement of depression was obtained with no major side effects.

Systematic indirect comparison of ospemifene versus local estrogens for vulvar and vaginal atrophy.

In the absence of a direct head-to-head study, we performed an indirect historical comparison of ospemifene 60 mg (Senshio®) vs. local vaginal estrogens in moderate or severe vulvar and vaginal atrophy (VVA). A literature search was carried out of clinical efficacy/safety trials of local vaginal estrogens in VVA approved in Europe. For efficacy comparison, studies had to be placebo-controlled and of 12 weeks' duration. For safety comparison, studies had to be ≥40 weeks' duration. Efficacy endpoints were the difference between active and placebo in change from baseline to week 12 for symptoms, vaginal pH, and maturation value (MV). Safety endpoints were endometrial safety, breast safety, thrombosis, and adverse events. The 12-week improvement over placebo in symptom score was not different for ospemifene 60 mg and 17ß-estradiol 10 µg and for ospemifene 60 mg and estriol gel. After 12 weeks, the percentages with vaginal pH <5.0 and <5.5 were better for ospemifene 60 mg than 10 µg 17ß-estradiol. Week-12 pH changes were comparable with estriol pessaries or gel and ospemifene 60 mg. The 12-week MV improvements over placebo were similar or better with ospemifene 60 mg compared with 10 µg 17ß-estradiol and with estriol pessaries or gel. There was no increased vaginal bleeding, endometrial hyperplasia, or carcinoma (including breast cancer) relative to placebo and no signal for increased risk of venous thromboembolism with ospemifene 60 mg or 10 µg 17ß-estradiol, but the confidence intervals for both products do not exclude an increased risk. This historical indirect comparison suggests that ospemifene 60 mg has an efficacy, safety, and tolerability profile comparable to or better than local vaginal estrogens in the treatment of VVA.

Fractional CO2 laser therapy: a new challenge for vulvovaginal atrophy in postmenopausal women.

OBJECTIVE: To evaluate the effects of CO2 laser in the treatment of vulvovaginal atrophy (VVA) in postmenopausal women. METHODS: VVA was assessed in 87 postmenopausal women (mean age 58.6 ± 6.9 years) before and after the treatment. The protocol consisted of three monthly treatments and included the treatment of vulva. Subjective measures included VAS (Visual Analog Scale) both for vaginal dryness and dyspareunia; DIVA (Day-by-day Impact of Vaginal Aging); a questionnaire on treatment satisfaction and one about the degree of pain during the procedure. Objective measures included VHI (Vaginal Health Index) and VVHI (Vulvo-Vaginal Health Index). Time points of the study were at the screening visit (T0), at baseline (T1), at week 4 (T2), at week 8 (T3), after 3 months since the last laser application (T4), after 6 months (T5), after 9 months (T6), after 12 months (T7) and after 15 months (T8). RESULTS: Treatment induced significant improvement in the VAS score. After treatment, VHI and VVHI indicated no VVA and this improvement was long lasting. Multivariate analysis showed that the time of follow-up was correlated with better VHI and VVHI (p < 0.001). DIVA improved over time (p < 0.001). CONCLUSIONS: This study shows that CO2 laser treatment induces a significant and long-lasting improvement of symptoms.

Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases?

Menopausal disorders may include shorter-term symptoms, such as hot flushes and night sweats (vasomotor symptoms, VMS) and longer-term chronic conditions such as cardiovascular disease (CVD), osteoporosis, and cognitive impairment. Initially, no clear link between the shorter-term symptoms and longer-term chronic conditions was evident and these disorders seemed to occur independently from each other. However, there is a growing body of evidence demonstrating that VMS may be a biomarker for chronic disease. In this review, the association between VMS and a range of chronic postmenopausal conditions including CVD, osteoporosis, and cognitive decline is discussed. Prevention of CVD in women, as for men, should be started early, and effective management of chronic disease in postmenopausal women has to start with the awareness that VMS during menopause are harbingers of things to come and should be treated accordingly.

Palliative care in patients with ovarian cancer and bowel obstruction.

OBJECTIVE: Malignant bowel obstruction (MBO) is usually a pre-terminal event in patients with ovarian cancer. However, because of the lack of data in literature, decisions around surgical intervention, non-resectional procedures, or medical treatment of MBO in patients with ovarian cancer cannot be lightly undertaken. We analyzed medical and surgical procedures, performance status, nutritional status, cachexia, and their prognostic value in this group of patients. METHODS: We retrospectively selected all consecutive patients with recurrent ovarian cancer who received medical or surgical treatment for MBO between October 2008 and January 2014 at the Academic Department of Gynecological Oncology of Mauriziano Hospital of Turin (Italy). RESULTS: We found 40 patients: 18 of them underwent medical treatment and 22 of them were submitted to surgery. In the group of surgery, the hospitalization was shorter (p 0.02), the pain reduction was more effective (p 0.001), the number of chemotherapy lines was higher (p 0.03), and re-obstruction was more rare (p 0.02). Between the two groups, we did not find any differences in post-palliation episodes of vomit (p 0.83), type of diet (p 0.34), ability to return home (p 0.72), and death setting (p 0.28). Median survival after palliation was longer in the group of surgery (p 0.025). Cachexia, low performance status, and poor nutritional status were significant predictors of worse survival after MBO, independently by the treatment. CONCLUSIONS: Surgery has to be considered in patients without serious contraindications; otherwise, a medical protocol, including antisecretory drugs, is the standard of care in frail patients.

Objective and self-reported cognitive dysfunction in breast cancer women treated with chemotherapy: a prospective study.

The objective of this study is to investigate if changes in cognitive functions can be recognised in patients undergoing chemotherapy for breast cancer. Forty women with breast cancer and without depression underwent cognitive evaluation before and after 6 months of chemotherapy; emotional evaluation was performed before and after 1, 3 and 6 months of chemotherapy. Self-reported cognitive deficit evaluation was included. Global cognitive functioning before starting chemotherapy was good. After 6 months of treatment there was a significant decline in some cognitive functions, particularly involving the attention subdomain. Objective cognitive deficit resulted independent from the emotional status. On the contrary, self-perceived mental dysfunction was unrelated to the objective cognitive decline, but it was associated with depression and anxiety. Breast cancer chemotherapy can induce domain-specific cognitive dysfunction. Patients' self-perception of mental decline is unrelated to objective cognitive deficit. Breast cancer patients negatively judge their cognitive performances if they have a negative emotional functioning.

Non-hormonal treatment of hot flushes in breast cancer survivors: gabapentin vs. vitamin E.

OBJECTIVES: To assess the efficacy and the tolerability of gabapentin 900 mg/day compared to vitamin E for the control of vasomotor symptoms in 115 women with breast cancer. The secondary objective was to evaluate the effect of the treatments on the quality of sleep and other aspects of the quality of life. METHODS: A hot flush diary was completed daily; sleep quality and other menopausal symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI), the Menopause Rating Scale (MRS) and the SF-36 Health Survey. RESULTS: The prescribed treatment with gabapentin was never started by 28.3% of the patients and was interrupted by 28% for side-effects (dizziness and somnolence). Among the women allocated to vitamin E, 16.36% never started therapy and 34.78% dropped out because of inefficacy. Hot flush frequency and score decreased by 57.05% and 66.87%, respectively (p < 0.05) in the gabapentin group. The effect of vitamin E was fairly small: hot flush frequency and score were reduced by 10.02% and 7.28%, respectively (p > 0.05). Gabapentin was also particularly effective in improving the quality of sleep (PSQI score reduction: 21.33%, p < 0.05). CONCLUSION: Gabapentin appears to be effective for the treatment of hot flushes with a favorable effect on quality of sleep. Vitamin E has only marginal effect on vasomotor symptoms.

Feasibility and oncological safety of sentinel node biopsy in breast cancer patients with a local recurrence.

OBJECTIVES: To investigate the role and feasibility of sentinel lymph node biopsy (SLNB) in breast cancer patients with a local recurrence and no clinically positive axillary lymph nodes. MATERIALS AND METHODS: A total of 71 patients underwent SLNB for breast cancer recurrence. At first surgery, they had received SLNB (46.5%), axillary lymph node dissection (ALND) (36.6%) or no axillary surgery (16.9%). RESULTS: Lymphatic migration was successful in 53 out of 71 patients (74.6%) and was significantly higher in patients with previous SLNB or no axillary surgery than in those with previous ALND (87.9% vs. 53.8%; p = 0.009). Aberrant lymphatic migration pathways were observed in 7 patients (13.2%). The surgical SLNB was successfully performed in 51 patients (71.8%). In 46 patients (90.2%) the SLN was histologically negative, in 3 patients (5.9%) micrometastastatic and in 2 patients (3.9%) macrometastatic. The 2 patients with a macrometastates in SLN underwent ALND, In 4 out of the 18 patients with failure of tracer migration ALND, performed as surgeon's choice, did not find any metastatic node. After a median follow-up period of 39 months (range: 2-182 months), no axillary recurrence has been diagnosed. CONCLUSION: A SLNB in patients with locally recurrent breast cancer, no previous ALND and negative axillary lymph nodes is technically feasible and impacts on the ALND rate. In patients who at primary surgery received ALND, migration rate is significantly lower, aberrant migration is frequent and no clinically useful information has been obtained.

Laparoscopic surgery in the treatment of stage I adult granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: Surgery represents the mainstay of treatment of stage I adult type granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent course of the disease, no prospective trials are available. Open surgery has long been considered the traditional approach; oncological safety of laparoscopy is only supported by small series or case reports. The aim of this study was to compare the oncological outcomes between laparoscopic and open surgery in stage I AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer) Group. METHODS: Data from patients with stage I AGCTs were retrospectively collected. Clinicopathological features were evaluated for association with relapse and death. Survival curves were calculated using the Kaplan-Meier method and compared with the log-rank test. The role of clinicopathological variables as prognostic factors for survival was evaluated using Cox's regression model. RESULTS: 223 patients were identified. Stage 1A, 1B and 1C were 61.5%, 1.3% and 29.6% respectively. 7.6% were apparently stage I. Surgical approach was laparoscopic for 93 patients (41.7%) and open for 130 (58.3%). 5-years DFS was 84% and 82%, 10-years DFS was 68% and 64% for the laparoscopic and open-group (p = 0.6).5-years OS was 100% and 99%, 10 years OS was 98% and 97% for the laparoscopic and open-surgery group (p = 0.8). At multivariate analyses stage IC, incomplete staging, site of primary surgery retained significant prognostic value. CONCLUSION: The present study suggests that surgical route does not affect the oncological safety of patients with stage I AGCTs, with comparable outcomes between laparoscopic and open approach.

Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of Surgical Oncology (SICO) Breast Oncoteam survey.

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014-2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy. In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations.

The influence of hormone replacement therapy on the pathology of breast cancer.

AIM OF THE STUDY: To assess whether the pathological characteristics of breast carcinomas arising in post-menopausal women who ever used hormonal replacement therapy (HRT) differ from those of post-menopausal patients who never used HRT. MATERIALS AND METHODS: Six hundred and forty three consecutive breast cancer patients were entered in a case control-study. Cases were represented by 111 breast cancer patients who had used or were using HRT at the time of diagnosis, while the remaining 532 patients who never used HRT were chosen as controls. RESULTS: Tumour diameter was smaller in HRT users (17.6 vs 22.1 mm; p=0.002) and tumours of lobular histology were almost twice more frequent among HRT users as in 'never users' (21 vs 12%; p=0.01). No differences were found in grading, hormonal receptor status and axillary nodal status. The expression of c-erb B-2, p53, Ki67 and PS2 measured by immunohistochemistry was similar in the two groups. CONCLUSIONS: Our findings suggest that HRT use may modify the pathological presentation of breast cancer. Further studies are indicated, while other clinical-pathological characteristics did not differ according to HRT use.

Evaluation of low-dose venlafaxine hydrochloride for the therapy of hot flushes in breast cancer survivors.

OBJECTIVE: To evaluate the efficacy and tolerability of long-term treatment with venlafaxine at low dose for the reduction of vasomotor symptoms in breast cancer survivors. DESIGN: Forty consecutive breast cancer patients suffering troublesome hot flushes have been treated for 8 weeks with venlafaxine XR 37.5 mg/day in an open-label study. Vasomotor symptoms have been evaluated before starting treatment and every 4 weeks with a hot flushes diary pointing out the number and the severity of vasomotor symptoms. A Beck Depression Inventory (BDI) was completed at baseline and at the end of the treatment. RESULTS: Thirty patients had completed the first 4 weeks of treatment, reporting a reduction of hot flushes frequency of 39% as compared to baseline (p<0.001). After 8 weeks of treatment, a further significant reduction was observed both for the hot flushes frequency (-53%; p<0.001) and for the hot flushes score (-59%; p<0.001), a measure which reflects both the number and the severity of hot flushes. Very few side effects were reported, mostly nausea in the first 2 weeks of assumption and mouth dryness. Only 23 women had completed BDI at week 8; a reduction of 23% was observed (p=0.000). CONCLUSION: Venlafaxine is an effective treatment for the relief of vasomotor symptoms in patients previously treated for breast cancer. A favourable effect is maintained also in those patients using tamoxifen as adjuvant therapy. The use of the low dose (37.5 mg/day) is associated with minimal side effects and produces a good improvement in hot flushes if pursued over 8 weeks.

Management of risk of breast carcinoma in postmenopausal women.

Breast carcinoma is the most frequent tumor in the female population. Many factors can influence the risk of breast cancer; some of them, such as old age and breast cancer 1/2 (BRCA1/BRCA2) gene mutations, are associated with a fourfold increase in risk. A previous diagnosis of atypical ductal or lobular hyperplasia or having a first-degree relative with a carcinoma are factors associated with a two- to fourfold increase in risk. A relative risk between 1 and 2 is associated with longer exposure to endogenous hormones as a result of early menarche, late menopause and obesity, or with recent and prolonged use of hormone replacement therapy (HRT) or with behavioural factors such as high alcohol and fat intake. Is it possible to modify breast cancer risk in postmenopausal women? Risk factors related to lifestyle can be changed, even if it is not clear whether modifying these behavioural factors during the postmenopausal period will influence the overall breast cancer risk. For instance, the influence of exogenous hormones throughout life (both oral contraceptives and HRT) should be evaluated according to the individual risk-benefit ratio. The problem is even more complex for women who carry genetic mutations and for those who have close relatives with breast cancer, who may be candidates for risk reduction strategies. Prophylactic bilateral mastectomy is still controversial, but is frequently offered to or requested by this group of women and may be indicated in BRCA1/BRCA2 carriers. Chemoprevention with tamoxifen and with the new selective estrogen receptor modulators, namely raloxifene, is very promising and deserves a thorough discussion for all high-risk women.

How to manage the menopause following therapy for breast cancer. is raloxifene a safe alternative?

Raloxifene is a selective oestrogen receptor modulator (SERM) that has anti-oestrogenic effects on breast and endometrial tissue and oestrogenic actions on bone, lipid metabolism and blood clotting. In postmenopausal women raloxifene decreases bone turnover and increases bone mineral density, reducing the incidence of vertebral fractures. Unlike tamoxifen, raloxifene does not cause endometrial hyperplasia or cancer, as demonstrated by endometrial monitoring with ultrasonography and biopsy during treatment. Evidence suggests that raloxifene lowers total low-density lipoprotein cholesterol levels behaving like oestrogens, but does not increase high-density lipoprotein cholesterol levels. In randomised clinical trials on postmenopausal women with osteoporosis, raloxifene reduced the risk of newly diagnosed ER-positive invasive breast cancer by 76% during a median of 40 months of treatment. However, raloxifene does not alleviate early menopausal symptoms, such as hot flushes and urogenital atrophy, and may even exacerbate some of them. In conclusion, raloxifene may be an alternative for the prevention of long-term effects of oestrogen deficiency (osteoporosis and heart diseases) in women with previous breast cancer not having hot flushes. For symptomatic patients, the association of raloxifene with different drugs which have demonstrated efficacy in the control of vasomotor symptoms is now under evaluation.

Clinical and ethical issues in the diagnosis of hereditary breast cancer (review).

A small subset of breast and ovarian cancers is related to the mutation of dominant susceptibility genes. The recent isolation of BRCA1 and BRCA2 has created great interest and expectations among members of families with a positive history for breast/ovarian cancer. We reviewed the literature to explore the clinical implications of genetic testing for BRCA1 and BRCA2 mutations among high risk women. Both the value of the information provided by the test and the efficacy of the preventive and diagnostic measures presently available have been examined. We also specifically address the issue of ethical dilemmas arising from widespread availability of genetic information, including psycological reactions of those who receive the test, genetic discrimination by health insurance companies or employers and prenatal testing for BRCA1 mutations.

Sentinel node dissection as definitive treatment for node negative breast cancer patients.

AIMS: Negative sentinel node may predict tumour-free axillary nodes in breast cancer. We report the performance of sentinel node dissection at our Institution. METHODS: We analysed data from 212 consecutive women with primary invasive breast tumours less than 3 cm in diameter and no axillary lymphadenopathy who underwent radioguided sentinel node dissection by means of 99mTc-colloidal albumin between 1999 and 2002. Completion axillary node dissection was performed if sentinel nodes contained metastases or if no sentinel nodes were identified. RESULTS: Sentinel nodes were identified in 207/212 of the patients. Fifty-seven patients had tumour-positive sentinel nodes. Only tumour diameter showed significant association with sentinel node status (p<0.000). Per-operative histologic evaluation had a sensitivity of 67.3% and a negative predictive value of 90.4%. No subset of sentinel node positive patients was identified for whom axillary node dissection could be safely avoided. No recurrences were detected at a median follow-up of 15 months. CONCLUSION: Radioguided sentinel node dissection offers a reliable way to assess nodal status in most breast cancer patients. In our experience, both preoperative lymphoscintigraphy and intraoperative histologic evaluation add useful information to the procedure.

Metabolic effects of tamoxifen in postmenopause.

Tamoxifen is actually considered the drug of choice for the hormonal treatment of early and metastatic breast cancer due to its efficacy and low toxicity. In addition, clinical trials of adjuvant therapy have demonstrated a 35% decrease in controlateral breast cancer in women receiving tamoxifen compared with controls, suggesting a potential role for this drug in chemoprevention of breast cancer in healthy women at increased risk of disease. Although tamoxifen is usually classified as an estrogen antagonist it also has partial estrogenic effects in some tissues such as liver, bone and uterus. The estrogenic action of tamoxifen on lipid metabolism and bone mineral density suggests additional benefits in protection against cardiovascular diseases and osteoporosis in postmenopausal women. Of particular interest could be the use of tamoxifen as an alternative to traditional estrogen replacement therapy in postmenopausal women previously treated for breast cancer or at increased risk of disease due to family history or histology on breast biopsy. The potential adverse effects of tamoxifen are partially similar to those of ERT and includes an increased risk of endometrial cancer, hepatic diseases, thromboembolic alterations and ocular toxicity. The mechanism of action of tamoxifen is briefly examined and the potential toxic effects and benefits of tamoxifen treatment are discussed.

Bone marrow micrometastases detected by a monoclonal antibody in patients with breast cancer.

One major problem in primary breast cancer is the identification of new parameters able to select patients at high risk of recurrence. Our study was aimed at detecting mammary tumor cells in the bone marrow of breast cancer patients using a single bone marrow sampling and the monoclonal antibody AB/3. This antibody recognizes a membrane carbohydrate epitope present in human breast cancer cells but not in normal tissues. Only 2 out of 45 breast cancer patients were found to have a bone marrow positive AB/3 staining reaction. Our data confirm and extend previous reports that single bone marrow sampling coupled with immunocytochemistry is not sensitive enough to be used as a routine procedure to acquire prognostic information in breast cancer.

TPS and CA 15.3 serum values as a guide for treating and monitoring breast cancer patients.

BACKGROUND: Tissue Polypeptide-specific Antigen (TPS) and CA 15.3 are two of the most widely studied tumor markers in the serum of breast cancer patients. TPS is a tumor associated proliferative marker which belongs to the cytoskeleton. CA 15.3 is a high molecular weight glycoprotein of clinical relevance in the monitoring of treatment and the detection of recurrence in breast cancer patients. PATIENTS AND METHODS: Serum values of TPS and CA 15.3 were measured in a prospective series of patients with primary breast cancer (n=267) and benign breast disease (n=46). The cut-off levels (95% specificity) determined for each test were 80 U/I for TPS and 30 k/U/l for CA 15.3. RESULTS: The diagnostic sensitivity was 0.31 for TPS and 0.32 for CA 15.3 for the detection of breast cancer. Serum TPS levels in breast cancer patients showed a relatively low positivity rate (33%), which was comparable with that of CA 15.3. Higher concentrations of TPS were found in cases with locally more advanced disease as well as in G3 tumors. By contrast, CA 15.3 basal levels were solely related to tumor size and nodal involvement. TPS and CA 15.3 levels were not related to estrogen and progesterone receptor status, peritumoral vessel invasion, multifocality and the in situ component of the tumor. After primary treatment, 20 patients developed distant metastases. In metastatic breast cancer patients TPS was more frequently and more markedly elevated than CA 15.3. In progressive disease, elevated values of TPS and CA 15.3 were found in 85% and 50%, respectively. The mean lead time was 10 months for TPS and 14 months for CA 15.3. Increasing values of TPS were independent of the site of metastasis, whereas elevated levels of CA 15.3 were mainly related to visceral metastasis. Local recurrences were usually associated with low levels of TPS and CA 15.3. By contrast, elevated values of TPS in locally recurred cases indicated rapidly progressive disease. CONCLUSIONS: Our study indicates that TPS and CA 15.3 are not helpful in distinguishing patients with breast cancer from patients with benign breast lesions. Nevertheless, at the time of diagnosis increased serum levels of the markers may facilitate the selection of high risk patients for whom additional treatment and careful follow up studies should be undertaken. Furthermore, TPS seems to be a reliable tumor marker for the early diagnosis of metastatic breast carcinoma independent of the site of metastasis, while increasing values of CA 15.3 are mainly related to visceral involvement.