Image-guided fine-needle aspiration cytology and flow cytometry phenotyping of neck lymphadenopathy for the diagnosis of recurrent lymphoma.

OBJECTIVE: In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography (US), US-guided fine-needle aspiration cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of recurrent lymphoma and (ii) whether these tools were independent predictors of correct results. DESIGN: Retrospective cohort study with stepwise forward logistic regression analysis of results. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 151 patients with a history of lymphoma who developed a cervical mass during follow-up. METHODS: On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. RESULTS: Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results (P = 0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.986). CONCLUSION: This minimally invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded.

Ultrasonic dissection system technology in breast cancer: a case-control study in a large cohort of patients requiring axillary dissection.

In the sentinel node era, axillary dissection (ALND) for breast cancer (BC) is required much less frequently than in the past. However, complications, such as prolonged drainage output and seroma formation, are still observed. Harmonic dissection devices (HDDs) are widely used in laparoscopic and minimally invasive surgery to reduce collateral damage during tissue dissection, but its usefulness in breast surgery is unclear. The aim of this study was to evaluate the efficacy of HDDs compared to that of conventional dissection in performing ALND. One hundred thirty-nine women (median age 61 years, range 34-71 years) with confirmed pT1-2 primary infiltrating ductal BC undergoing curative surgery were enrolled in the study. The population was prospectively randomized between two age- and stage-matched arms: group A (cases)-68 (48.9 %) patients (HDD technique), versus group B (controls)-71 (51.1 %) patients (conventional technique). In group B, skin flaps were obtained using a scalpel, scissors, and electrocautery which was never used for ALND. In group A, for each operation time, the HDDs were used exclusively. The mean operative time, intraoperative blood loss, and drainage output were (A vs. B) 95 ± 22 versus 109 ± 25 min, 56 ± 12 versus 86 ± 15 mL, and 412 ± 83 versus 456 ± 69 mL, respectively (p < 0.01). Twenty-nine (20.9 %) patients developed an axillary seroma: 9 (13.2 %) and 20 (28.2 %) for groups A and B, respectively (p = 0.030). Our study confirms that in patients with BC requiring ALND the use of HDDs is more time efficient than conventional surgery, and reduces intraoperative bleeding, the amount of drainage, and the risk of seroma formation. These results may lead to several short- and long-term advantages. Thus, a careful evaluation of the cost-benefits of nontraditional tools, such as HDDs, should be performed in all patients undergoing modified radical or partial mastectomy and ALND for BC.

Treatment of estrogen receptor-positive breast cancer.

Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive. The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.

Calcium metabolism & hypercalcemia in adults.

Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly depends on the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negative feed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroid cells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been considered the main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho, and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accounting for more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubular function) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, and heart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequences in the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specific and addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.

Imaging studies in hypercalcemia.

Hypercalcemia is a relatively common clinical problem, mainly (>90%) related to primary hyperparathyroidism (HPT) and malignancies. The anatomical and functional imaging techniques available for locating enlarged parathyroid glands include ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine imaging techniques. The most commonly employed are US and parathyroid scintigraphy, while CT, MRI, positron emission tomography (PET)/CT, and selective venous sampling are generally used in patients with persistent or recurrent HPT, or when findings of non-invasive studies are negative or conflicting. The reported accuracy is 57-93%, 54-93%, and up to 95% for US, (99m)Tc-sestamibi scintigraphy, and the two modalities combined, respectively. A multimodality approach (x-ray, whole-body scintigraphy, CT, MRI, and PET) is usually recommended for whole body assessment in cases of cancer-induced hypercalcemia (CIH). Imaging studies should evaluate each organ (i.e. breast, kidney, prostate, parathyroid) potentially involved in the pathogenesis of hypercalcemia in patients with CIH. In cases of skeletal metastases, when findings on plain x-ray or bone scans are uncertain, any unexplained region of abnormal uptake should be examined by MRI and/or ¹8F-fluoro-2- deoxyglucose (FDG)-PET/CT, which has proved more accurate than classical bone scintigraphy, especially for dealing with hematologic malignancies. A number of radionuclide tracers, other than ¹8F-FDG, are available for use in selected cases to locate specific tumors (i.e. 68Ga for neuroendocrine tumors). This is a review of recently published information on the imaging techniques currently available for patients with hypercalcemia.

Endocrine therapy of breast cancer.

Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.

Relationship between body mass index, age and hypoxemia in patients with extremely severe obesity undergoing bariatric surgery.

BACKGROUND: Morbid obesity is frequently accompanied by serious co-morbidity, enclosed obstructive sleep apnea and hypoventilation syndrome, and thus many morbidly obese patients require surgical interventions. The aim of this study was to evaluate the relationship between arterial oxygen (pO2) and carbon dioxide (pCO2) partial pressure, age, loss of excess weight, and body mass index (BMI) in obese patients scheduled to undergo bariatric surgery. PATIENTS AND METHODS: A group of 11 patients (4 men, 7 women, median age 38 years, range 23-58 years) with extremely severe obesity (BMI>50 kg/m²) underwent laparoscopic Roux-en-Y gastric bypass. Preoperatively, BMI, pO2, and pCO2 were 52.7±2.4 kg/m², and 70.9±5.3 and 43.1±6.5 mmHg, respectively. Hypoxemia (pO2<75 mmHg) was present in all patients, but no relationship between BMI and age (R=-0.24, p=0.44) or between BMI and pO2 (R=0.09, p=0.77) was found. RESULTS: As expected, there was a significant correlation between age and both pO2 (R=-0.58, p=0.04) and pCO2 (R=0.85, p=0.0004), while no relationship between BMI and age (R=-0.24, p=0.44), nor between BMI and pO2 (R=0.09, p=0.77) was found. Finally, there was a significant correlation between pO2 and loss of excess weight (R=-0.69, p=0.02). No intra- or postoperative complications were observed, and 12 months after surgery BMI decreased to 32.5±2.7 kg/m² (p<0.001) and pCO2 to 37.9±5.3 mmHg (p=0.05), while pO2 reached 85.8±6.8 (p<0.001) mmHg. CONCLUSIONS: In obese patients, the severity of hypoxemia is mainly related to age. The amount of weight reduction, rather than lower baseline BMI values, may justify the significant postoperative pO2 improvement.

Medical Treatment of Hirsutism in Women

Hirsutism is the presence of excess hair growth in women in the typical male hair growth areas, thereby reflecting a deviation from the normal female hair pattern. It affects from 5% to 10% of women, depending on age, menopausal status and ethnic background. The presence of hirsutism is very distressing for women, and subsequently may have a negative impact on their psychosocial life. In the treatment of hirsutism several options are now available, including pharmacologic regimens and cosmetic measures. Both the hormonal profile of the patient and her expectations and preferences should guide the therapeutic approach. The aims of the medical therapy are suppression of excessive androgen production, inhibition of peripheral action of androgens, and treatment of patients at risk for metabolic disorders or reproductive cancers. For other diseases related to endocrine abnormalities, such as thyroid disorders or Cushing's syndrome, specific treatment is mandatory. After an ineffective local approach by direct hair removal, a pharmacological treatment should be suggested, using estrogen and progestin combinations, antiandrogens (i.e. cyproterone acetate, spironolactone) or both as a first line. Finasteride, gonadotropin-releasing hormone agonists, and glucocorticoids should be used in selected cases. Adequate contraception is also recommended if antiandrogens are used. Unfortunately, since systemic therapy reduces hair growth in less than 50% of cases, hirsute women frequently require cosmetic measures. The use of a logical combination of different options has been shown to achieve a satisfactory result in most cases. This review provides information and suggestions about the current options of treating hirsutism.

Relationship between prognostic factors of breast cancer and 99mTc-sestamibi uptake in patients who underwent scintimammography: Multivariate analysis of causes of false-negative results.

The complementary role of sestamibi scintimammography (SSM) in patients with breast cancer (BC) is well established. The aim of this study was to establish whether a relationship exists between sestamibi uptake, evaluated as a tumour-to-background ratio (TBR), and the main prognostic factors of BC. SSM with the measurement of TBR was performed preoperatively in 102 women (median age 57 years, range 32-81 years) who underwent curative surgery for primary BC. Final pathology showed 4 (3.9%) with pT1a, 17 (16.7%) with pT1b, 44 (43.1%) with pT1c and 37 (36.3%) with pT2 breast carcinomas. The overall sensitivity of SSM was 80.4%. An ANOVA showed significant (P<0.01) differences between the TBR of patients with G1 vs. G3 tumours, and between the TBR of those with G2 vs. G3 breast carcinomas. Moreover, there was a difference (P=0.021) between the TBR of patients (n=12, 11.8%) with CEA serum levels >10 ng/ml (2.031+/-0.420), and those with normal (n=90, 88.2%) CEA values (1.713+/-0.446), whilst no difference (P=NS) was found between patients (n=27, 26.5%) with CA 15-3 >30 U/ml (1.893+/-0.401) and those with normal (n=75, 73.5%) CA 15-3 values (1.699+/-0.462). There was a mild inverse correlation between TBR and both the oestrogen (R=0.25, P=0.011) and the progesterone receptor (R=0.23, P=0.02) rate. The logistic regression analysis showed that only size and CA 15-3 serum levels represent true independent parameters, but the function was able to predict only 11 out of 21 (52.4%) patients with false-negative SSM. TBR is independent of age and mainly correlates with the size of the tumour. There are no reliable preoperative prognostic factors that are really useful for improving SSM sensitivity in patients with small breast carcinomas.

Relationship of AgNOR counts and nuclear DNA content to survival in patients with parathyroid carcinoma.

The aim of this study was to evaluate the usefulness of DNA flow cytometry to determine tumor nuclear DNA index (DI), and nucleolar organizer region protein counts visualized by the argyrophil (AgNOR) technique, in confirming diagnosis and predicting clinical outcome of patients with parathyroid carcinoma (PC). We reviewed paraffin-embedded tissue sections, from 15 patients (median age 63 years, range 30-68 years) with PC who died of the disease, which were randomly compared with tissue sections from 15 age- and sex-matched patients with parathyroid adenoma (PA). The proliferative activity in parathyroid tumours as detected by DI and AgNOR counts was evaluated in all specimens. Both DI (1.37 +/- 0.33 vs 1.0 +/- 0.1) and AgNOR (3.01 +/- 0.31 vs 1.54 +/- 0.35) counts were higher (P < 0.001) (Student's t-test) in patients with PC than in those with PA. Diploid (DI = 1), aneuploid (DI > 1) and hypoploid (DI < 1) neoplasms were found in 11 (PC = 4, PA = 7), 14 (PC = 11, PA = 3) and five (PC = 0, PA = 5) patients respectively. The average postoperative survival in patients with PC was 46.9 +/- 37.4 months (range 21-146 months). The survivals of patients with aneuploid (n = 11) and diploid (n = 4) PC were 74.0 +/- 58.1 and 34.1 +/- 18.4 months (P=0.21) respectively. There was a significant relationship between DI and AgNOR counts (R=0.69, P < 0.01), but no correlation was found between survival and both DI (Rho = 0.17, P = 0.55) and AgNOR counts (Rho = 0.26, P = 0.35). Moreover, there was no correlation (P = NS) between the main preoperative biochemical parameters and survival. In conclusion, DI and AgNOR are useful in confirming the diagnosis of PC, but they are of little value in predicting the clinical outcome of patients with PC.

Seroma prevention following axillary dissection in patients with breast cancer by using ultrasound scissors: a prospective clinical study.

AIMS: Seroma formation following axillary dissection is a common complication of breast surgery. The aims of this study were (1) to analyse the risk factors of seroma formation, and (2) to evaluate the role of ultrasound scissors in performing axillary dissection in patients with primary breast cancer undergoing mastectomy and breast-conserving surgery. METHODS: Ninety-two women (median age 55 years, range 33-73 years) requiring surgery for known unilateral primary breast cancer (pT1a=1, pT1b=20, pT1c=43, pT2=25, pT3=3) were prospectively randomised to undergo axillary dissection by either using (Group A, 45 patients) or not using (Group B, 47 patients) ultrasound scissors (US). Thirty-eight (41.3%) patients underwent modified radical mastectomy, while 54 (58.7%) underwent breast-conserving surgery. RESULTS: Twenty-eight (30.4%) patients (Group A=9 out of 45, 20%; Group B=19 out of 47, 42%; P=NS) developed a wound seroma. Multivariate analysis using a logistic regression model showed that surgical procedure (RR=8.9; 95% CI: 3.2-25.3), total amount of drainage (RR=7.8; 95% CI: 2.8-22.0), and size of the tumour (RR=6.0; 95% CI: 2.2-16.5) independently correlated with seroma formation. The logistic regression function (RR=19.4; 95% CI: 6-62) correctly allocated 75 out of 92 (81.5%) patients. CONCLUSIONS: Size of the tumour, and total amount of drainage represent the principal factors of seroma formation following axillary dissection in patients undergoing surgery for breast cancer. Although the use of ultrasound cutting devices may reduce the risk of seroma formation, further studies are need to verify the real impact on long-term morbidity of such technique.

Short- and long-term changes in bone mineral density of the lumbar spine after parathyroidectomy in patients with primary hyperparathyroidism.

The aims of this study were (1) to analyze whether correlations exist between lumbar spine (LS) bone mineral density (BMD) and the main preoperative biochemical parameters in a large population of patients with primary hyperparathyroidism (HPT); and (2) to evaluate the LS-BMD changes after parathyroidectomy (PTx) at long-term follow-up. Sixty-two patients (median age 57 years, range 23-82 years) with confirmed primary HPT underwent LS osteodensitometry by dual-energy X-ray absorptiometry with BMD measurements at the L2-L4 region before surgery and at 1 year and 2 years after successful PTx. Three groups of patients were considered: Group A (men, n = 14, 22.6%), Group B (premenopausal women, n = 12, 19.3%), and Group C (postmenopausal women, n = 36, 58.1%). There were no linear correlations (P = NS) among the main biochemical parameters, the age of the patients, and their baseline LS-BMD values that were significantly (P < 0.01) lower in Group C patients. At 2-year follow-up the LS-BMD improved by 13.0%, 11.5%, and 11.7% in Groups A, B, and C, respectively (P = NS). In order to compare groups with the same linear relationship between age and LS-BMD, a subgroup of postmenopausal patients aged < or = 60 years (Group C2) was considered. ANOVA showed that the improvement of the LS-BMD at 1- and 2-year follow-up was higher (P = 0.002) in Group B than in Group C2 patients. The result was confirmed by using the Mann-Whitney U-test (P = 0.0078). Improvement of LS-BMD after successful PTx was significantly (P < 0.01) higher in premenopausal women, suggesting a possible role of estrogen hormone in complete bone remodeling.

CT-scan, MRI and image-guided FNA cytology of incidental adrenal masses.

AIM: The aim of this study was to compare the usefulness of computed tomography (CT)-scan, magnetic resonance imaging (MRI), and fine-needle aspiration (FNA) cytology in patients with incidentally discovered adrenal masses. PATIENTS AND METHODS: Thirty-four consecutive patients (six men and 28 women, median age of 47 years, range 26-80) with non-functioning adrenal masses of 2 cm or more (median 3.5 cm, range 2-9) were studied. All patients underwent CT-scan, MRI, and image-guided FNA cytology using spinal-type narrow-gauge needles prior to further procedures. Nineteen patients underwent adrenalectomy. RESULTS: Final pathology showed 13 benign adrenal lesions, four adrenocortical carcinomas, and two unsuspected adrenal metastases. Fifteen patients who did not have surgery were considered definitively as having benign adrenal lesions since the mass was unchanged on CT-scans performed during follow-up. The sensitivity, specificity, and positive predictive value were 66.7, 85.7, and 50.0%, for CT-scan, 83.3, 92.9, and 71.4% for MRI, and 83.3, 100, and 100% (p<0.05) for FNA cytology, respectively. CONCLUSIONS: Image-guided FNA cytology is a safe and sensitive procedure that may reveal unsuspected adrenal malignancies, and should be performed in all patients with incidentally discovered adrenal masses of more than 2 cm in size.

Breast cancer risk in healthy and symptomatic women: results of a multivariate analysis. A case-control study.

Several risk factors for breast cancer (BC) have been investigated in different reports, but none has been really useful in preventing BC development. The aim of this study was to evaluate the risk of BC in self-selected symptomatic women in comparison with the healthy population residing in an urban area of Italy. A group of 404 women (median age 59 years, range 26-89 years) with confirmed BC (cases) were age-matched with 389 healthy women (Group A), and 391 (Group B) symptomatic non-screened patients without BC, who were referred to our Breast unit. The results of univariate analysis showed a significant (P < 0.01) difference between cases and controls in (1) age at menarche, (2) number of birth and age at first births, (3) lactation and months of lactation, and (4) estrogen replacement therapy (ERT) and duration of ERT. Multivariate analysis using a logistic regression model adjusted for age showed that five independent parameters (no pregnancy, age at first birth > 30 years, no lactation, use of ERT, ERT > 40 months) significantly (P < 0.01) correlated with BC onset. The relative odds ratios (ORs) at 95% confidence interval (95% CI) were 5.25, 2.47, 2.82, 2.80, and 5.56, respectively. The cumulative OR (95% CI) calculated from the observed vs. predicted values was 7.15. No differences (P = NS) were found between groups A and B. In conclusion, in our study population, the prolonged use (> 40 months) of ETR in menopausal women resulted in an increased risk of BC, and represented the only risk factor that could be removed.

Relationship between serum parathyroid hormone, serum calcium and arterial blood pressure in patients with primary hyperparathyroidism: results of a multivariate analysis.

OBJECTIVE: To evaluate the possible relationship between serum calcium, serum parathyroid hormone (PTH) levels and arterial blood pressure (BP) in patients with primary hyperparathyroidism (HPT). DESIGN: A retrospective population-based study. METHODS: Charts of 194 patients with proven primary HPT were reviewed, and the main clinical and biochemical parameters were recorded. There were 48 men (24.7%) and 146 women (75.3%), with a median age of 59 years (range 23-82 years). Patients who used antihypertensive drugs or hormone replacement therapy had been previously excluded. All patients underwent successful parathyroidectomy, and were cured of their disease. RESULTS: There were no differences (P=NS) between men and women in systolic (143.3+/-19.1 vs 145.4+/-17.1 mmHg) and diastolic (87.1+/-12.3 vs 88.4+/-9.9 mmHg) BP, and in the main biochemical parameters. A significant (P<0.01) correlation was found between (i) serum calcium and serum PTH levels (r=0.39, F=88.36), (ii) age and BP, both systolic (r=0.61, F=118.16) and diastolic (r=0.48, F=64.5), and (iii) body mass index (BMI) and BP (r=0.45 and 0.36 respectively). There was no significant association of serum calcium levels with systolic (r=0.0974, t=1.3422, P=0.18) or diastolic (r=0.1117, t=1.5409, P=0.12) BP, and of serum PTH levels with systolic (r=-0.0349, t=-0.4783, P=0.63) or diastolic (r=-0.0793, t=-1.0913, P=0.28) BP. Multivariate analysis confirmed that none of the independent biochemical parameters significantly correlated with BP, both systolic and diastolic. CONCLUSIONS: In patients with primary HPT there is no relationship between PTH, calcium and BP. Thus, in hyperparathyroid patients, BP should be considered as an independent variable, mainly related to age and BMI.

Breast complaints and risk of breast cancer. Population-based study of 2,879 self-selected women and long-term follow-up.

The aim of this study was to provide information about risk of breast cancer (BC) in women with breast complaints undergoing spontaneously clinical examination. The records of 2,879 self-selected symptomatic new patients observed consecutively were reviewed, and the chief breast complaint such as pain, lump and nipple discharge had been recorded. Patients were divided in three groups: Group A, 1,186 (41.2%) patients aged < 41 years; Group B, 809 (28.1%) patients aged 41-55 years; and Group C, 884 (30.7%) patients aged > 55 years. Pain was most common (P < 0.01) in Group A (60.8%), and lump in Groups B (53.3%) and C (89.7%). A total of 318 (11.0%) women had histologically confirmed BC (Group A = 3.5%, Group B = 30.5%, Group C = 66.0%), accounting for 3.2, 16.4 and 12.0% of patients with pain, lump and nipple discharge, respectively. Breast complaints were equally (P= NS) distributed between patients with and without BC. The relative risk (RR) of BC developing ranged between 0.5-1.4, 0.5-1.9, and 0.6-3.0 in Groups A, B, and C, respectively. It ranged between 0.3 and 0.7 in patients with breast pain, and was significantly higher (RR = 1.9-3.0) only in patients with breast lump aged > 40 years. In conclusion, in symptomatic patients BC risk is strictly related to age, and independent of the referred symptoms. Therefore, further investigations have to be warranted only when risk factors different from breast complaints are present.