Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.

Incidence of inactive allele CYP2D6*4 among Greek women suffering from hormone-sensitive breast cancer.

BACKGROUND: The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The aim of the present study is to estimate the incidence of CYP2D6*4, in the Greek population and more precisely among females suffering from breast cancer. MATERIALS AND METHODS: Eighty unrelated mainland Greek female volunteers suffering from hormone-sensitive breast cancer were recruited during their primary handling or follow-up examination in order to provide samples for purification and polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) of genomic DNA derived from buccal swabs. RESULTS: The incidence of individuals with at least one present allele*4 within the Hellenic population was estimated to be as high as 30% (n = 24/80), with a 95% confidence interval of 20% to 40%. From the statistical point of view, it can be securely stated that incidence of *4 among Greek women is over 20%. The incidence of homozygous carriers of *4 in the present sample occurred in 8.75%, while the incidence of allele*4 haplo-type occurred in 19.4% (n=160). CONCLUSION: Although the outcoming results for Greek women are actually in line with existing data for other European nations, it should be noted, that a routine CYP2D6 testing of women suffering from breast cancer is formally not recommended, as the clinical significance of CYP2D6 phenotype in treatment and outcome of breast cancer remains unclear.

Time dependence of biomarkers: non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer.

BACKGROUND: We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial. METHODS: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years. RESULTS: We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P<0.05), with increases in R(2) between 5 and 6% and increases in D-statistic between 0.16 and 0.21. CONCLUSIONS: Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy.

Do type 1 receptor tyrosine kinases inform treatment choice? A prospectively planned analysis of the TEAM trial.

BACKGROUND: Epidermal growth factor receptors contribute to breast cancer relapse during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve outcomes in HER-positive cancers. METHODS: Tissue microarrays were constructed. Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed relative to disease-free survival and treatment using outcomes at 2.75 and 6.5 years. RESULTS: Among 4541 eligible samples, 4225 (93%) had complete HER1-3 data. Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32% (n=1351) overexpressed at least one HER receptor. In the HER1-3-negative subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years was 0.67 (95% confidence interval (CI), 0.52-0.87), in the HER1-3-positive subgroup, the HR was 1.15 (95% CI, 0.85-1.56). A prospectively planned treatment-by-marker analysis demonstrated a significant interaction between HER1-3 and treatment at 2.75 years (HR=0.58; 95% CI, 0.39-0.87; P=0.008), as confirmed by multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95% CI, 0.36-0.85; P=0.005). This effect was time dependent. CONCLUSION: In the 2.75 years prior to switching patients initially treated with tamoxifen to exemestane, a significant treatment-by-marker effect exists between AI/tamoxifen treatment and HER1-3 expression, suggesting HER expression could be used to select appropriate endocrine treatment at diagnosis to prevent or delay early relapses.

Seasonal variation in breast cancer incidence. Circumstantial or default event?

UNLABELLED: It has been previously suggested that seasonality in the detection of breast cancer is mostly seen in countries with distinct climatic variations. Patient characteristics and delays have been implicated in the etiology of peak presentation. Seasonality has been more marked in premenopausal women, while delays have been attributed to both patients and health care systems. PATIENTS: A total of 1,411 women who presented with breast cancer to our department were analyzed according to their age, menopausal status, site, stage, grade, ER and PR status, c-erb-2 and Ki-67 (412) during the year. RESULTS: The seasonal variation was statistically significant, but no statistically significant differences were established between corresponding subgroups. CONCLUSION: The seasonal variation most probably reflects temporal, psychosocial and behavioral patterns in the Greek female population. Since we do not have the ability to recognize the actual onset of any cancer and then correlate it with various different independent factors we can not correlate its influence on survival or biological marker manifestations.

Variations in locoregional therapy in postmenopausal patients with early breast cancer treated in different countries.

BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial is an international randomized trial evaluating the efficacy and safety of exemestane, alone or following tamoxifen. The large number of patients already recruited offered the opportunity to explore locoregional treatment practices between countries. METHODS: Patients were enrolled in Belgium, France, Germany, Greece, Ireland, Japan, the Netherlands, the UK and the USA. The core protocol had minor differences in eligibility criteria between countries, reflecting variations in national guidelines and practice regarding adjuvant endocrine therapy. RESULTS: Between 2001 and 2006, 9779 patients of mean(s.d.) age 64(9) years were randomized. Some 58.4 per cent had T1 tumours (range between countries 36.8-75.9 per cent; P < 0.001) and 47.3 per cent were axillary node positive (range 25.9-84.6 per cent; P < 0.001). Independent factors for type of breast surgery were country, age, tumour status and calendar year of surgery. After breast-conserving surgery, radiotherapy was given to 93.2 per cent of patients, 86.0 per cent in the USA and 100 per cent in France. Axillary lymph node dissection was performed in 82.0 (range 74.6-99.1) per cent. CONCLUSION: Despite international consensus guidelines, wide global variations were observed in treatment practices of early breast cancer. There should be further efforts to optimize locoregional treatment for breast cancer worldwide.

Multigene assays in early breast cancer: Insights from recent phase 3 studies.

Multigene assays (MGAs) guide treatment in early-stage breast cancer (ESBC) enabling selective and effective use of adjuvant chemotherapy (CT). Support for all MGAs had previously been derived from retrospectively-analyzed, prospective studies. Only 2 ESBC MGAs, the 70-gene signature (MammaPrint®) and the 21-gene Recurrence Score (RS) assay (Oncotype DX®), are now supported by entirely prospective randomized phase 3 trials. These studies varied in their primary objectives, design, and eligibility. The MINDACT study provided the first level 1 evidence for the 70-gene signature, identifying a prognostic capability irrespective of lymph node (LN) or hormone receptor (HR) status. However, the study did not support predictive value for the assay regarding adjuvant CT utility. The second prospective study, WSG-PlanB, confirmed the prognostic value of the 21-gene RS assay in HR-positive tumors with RS ≤ 11. A 5-year disease free survival (DFS) of 94% was identified in this group when treated with endocrine therapy (ET) alone regardless of N0 or N1 nodal status. The final new prospective study, TAILORx, confirmed the prognostic value of the 21-gene assay in N0 HR-positive disease, demonstrating a lack of CT benefit in patients with midrange RS. The information from these phase 3 studies confirms that MGAs are not interchangeable and that each provides different information for differing patient populations. Prognosis-only is supported for the 70-gene signature while both prognosis and the predictive value of CT are provided by the 21-gene assay. This review assesses and contrasts these phase 3 studies in the context of target populations and clinical utility.

Lipid changes in breast cancer patients on exemestane treatment: final results of the TEAM Greek substudy.

BACKGROUND: The Greek substudy of the Tamoxifen and Exemestane Adjuvant Multicenter International trial compared the effect of exemestane on the lipid profile of postmenopausal, breast cancer patients to that of tamoxifen in the adjuvant setting. PATIENTS AND METHODS: Lipidemic profile changes were studied in 142 postmenopausal patients randomized to receive either adjuvant exemestane (n=77) or tamoxifen (n=65). Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum triglyceride (TRG) levels were measured at baseline and then every 3 months for the first 12 months of treatment and at 18 and 24 months. RESULTS: A trend for a reduction in TC was found in both treatment arms; however, TC and LDL levels were consistently and significantly decreased in tamoxifen arm only. The mean HDL level was higher for the tamoxifen arm compared with the exemestane arm across time. No significant trend was detected throughout the study period on TRG levels on either arm. CONCLUSIONS: Unlike tamoxifen's beneficial effect on TC and LDL levels, exemestane appears to have a neutral effect on lipidemic profile of postmenopausal, breast cancer patients. These data offer additional information with regard to the safety and tolerability of exemestane treatment in the adjuvant setting.

Impact of breast cancer surgery on the self-esteem and sexual life of female patients.

Patient satisfaction with cosmetic outcome and the psychological impact of breast cancer surgery were evaluated. A total of 207 patients with primary breast cancer, treated with either breast-conserving surgery (n = 83), modified radical mastectomy without reconstruction (n = 108), or mastectomy with delayed breast reconstruction (n = 16) rated their cosmetic outcome and satisfaction following surgery, and the impact of surgery on their self-esteem and sexual life, by questionnaire. Patients undergoing breast-conserving surgery were most satisfied with their surgery and body image, followed by those treated with mastectomy with delayed reconstruction. Although diagnosis of breast cancer had a negative impact on the psychology of all patients, those undergoing breast-conserving surgery or mastectomy with delayed reconstruction were more satisfied and reported a lower impact on their self-esteem and sexual life versus those who only had mastectomy. Diagnosis of breast cancer has a negative psychological impact on the patient, but the type of surgery has a significant role in post-operative self-esteem and sexual life.

Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00.

BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was conducted, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. The safety analysis is presented. PATIENTS AND METHODS: From October 2000 until June 2005, 1121 node-positive patients were randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of 'intensified' combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen.

Impact of age on breast cancer mortality and competing causes of death at 10 years follow-up in the adjuvant TEAM trial.

AIM: Due to increasing life expectancy, patients with breast cancer remain at risk of dying due to breast cancer over a long time. This study aims to assess the impact of age on breast cancer mortality and other cause mortality 10 years after diagnosis. METHODS: Postmenopausal patients with hormone-receptor positive breast cancer were included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. Age at diagnosis was categorised as <65 years (n = 3369), 65-74 years (n = 1896) and ≥75 years (n = 854). Breast cancer mortality was assessed considering other cause mortality as competing event using competing risk analysis. RESULTS: After a median follow-up of 9.8 years (interquartile range 8.0-10.3), cumulative incidence of breast cancer mortality increased with increasing age (age <65 years, 11.7% [95% confidence interval {CI}: 10.2-13.2]; 65-74 years, 12.7% (11.2-14.2) and ≥75 years, 15.6% (13.1-18.0)). Univariate subdistribution hazard ratio (sHR) increased with increasing age (age: 65-74 years, sHR: 1.08, 95% CI: 0.92-1.27 and ≥75 years sHR: 1.30, 95% CI: 1.06-1.58, P = 0.013). Multivariable sHR adjusted for tumour and treatment characteristics increased with age but did not reach significance (age 65-74 years, sHR: 1.11, 95% CI: 0.94-1.31; ≥75 years, sHR: 1.18, 95% CI: 0.94-1.48, P = 0.055). CONCLUSION: Ten years after diagnosis, older age at diagnosis is associated with increasing breast cancer mortality in univariate analysis, but it did not reach significance in multivariable analysis. This is not outweighed by a substantially higher other cause mortality with older age. This underlines the need to improve the balance between undertreatment and overtreatment in older patients with breast cancer. The trial was registered in International Trial Databases (ClinicalTrials.govNCT00279448, NCT00032136, and NCT00036270; the Netherlands Trial Registry NTR267).

Breast cancer risk in relation to most prevalent IgE specific antibodies: a case control study in Greece.

BACKGROUND: This study aims to explore the debatable role of allergy in breast cancer (BC) by using country-specific biological markers, namely levels of the most prevalent allergen-specific immunoglobulin E in Greece. PATIENTS AND METHODS: Blood samples and clinical information were collected over a 30-month period from 103 women with histologically-confirmed BC and 103 controls from two university hospitals in Athens. Allergen-specific IgE, against the 12 prevailing allergens in Greece were determined; thereafter, a score comprising the sum of the individual values for this battery of serological IgE determinations was created. Bivariate and multiple logistic regression analyses were undertaken using case-control status as the outcome and IgE-scores as the predictor variable, controlling for socio-demographic, gynecological and lifestyle confounders. RESULTS: The serum IgE score seemed to be positively related to BC (OR: approximately 1.73; CI: 0.95-3.14; p-value: 0.07). A positive correlation between serological evidence and allergic history among controls was also found (p-value: 0.06). CONCLUSION: This investigation suggests an IgE-mediated allergic response among women with BC in comparison to their controls. The finding needs confirmation by immuno-epidemiological investigation to clarify the directionality of this association and whether laboratory-ascertained atopy can be considered as a risk-marker of susceptibility in the development of BC.

Mitoxantrone plus vinorelbine in pretreated patients with metastatic breast cancer.

Vinorelbine and mitoxantrone have both been demonstrated to have significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of the combination as second or third line treatment in patients with metastatic breast cancer (MBC). Fifty-one previously treated patients with MBC were enrolled from October 2001 to May 2004 and 48 were eligible for evaluation. Median age was 59 years (range 33-82) and ECOG performance status was < or =2. Distant sites of metastasis were as follows: liver 64%, bone 49%, lung 36%, lymph nodes 6%, skin 4%, brain 2% and other sites 6%. All patients received vinorelbine 20 mg/m(2), D1+8 and mitoxantrone 10 mg/m(2) D8 every 21 days for 6 cycles. All eligible patients were analyzed for toxicity and response. Two patients (4%) achieved complete response and 12 (25.5%) partial response. The objective overall response rate was 29.5% (95% confidence interval [CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%) had progressive disease and 7 (15%) were non-evaluable. After a median follow up of 18 months, overall survival was 13 months (range 0.8 - 38+) and median time to disease progression was 5 months (range 1 - 32). A total of 280 cycles was delivered. The relative dose intensities of mitoxantrone and vinorelbine were 79% and 77%, respectively. Toxicities (grade III-IV) were as follows: leukopenia 18 (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2 (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient. There were no treatment related deaths. The combination of mitoxantrone and vinorelbine is an effective regimen with manageable toxicity in pretreated patients with advanced breast cancer.

Clinical evidence supporting genomic tests in early breast cancer: Do all genomic tests provide the same information?

Breast cancer (BC) has historically been treated as a single disease entity; however, in the last decade, insights into its molecular heterogeneity have underpinned the development/commercialisation of several genomic tools whose goal is to guide patient management in early BC. These include the Oncotype DX® Breast Recurrence Score™ assay, MammaPrint®, Prosigna®, and EndoPredict®. Although these assays are similar in that they are all multigene assays reflecting risk of recurrence, they differ substantially in the technological platform used to measure gene expression; the number and identity of genes assessed; the patient populations used for development and validation; and the level of evidence supporting clinical utility. They also differ in the amount of evidence demonstrating their impact on treatment decisions and cost effectiveness in different countries. This review discusses these 4 assays, highlighting the clinical evidence that supports each of them, while focussing on the Recurrence Score assay. This assay has the greatest body of evidence supporting its clinical utility and decision impact/effectiveness, and currently is the only one validated as a predictor of response to adjuvant chemotherapy in hormone-receptor positive early BC patients treated with endocrine therapy and to be included as such in international/national BC treatment guidelines. The review also discusses ongoing prospective trials investigating the 4 assays, recent outcome studies, as well as analyses comparing different assays on the same tumour blocks.

Paraffinomas of the breast or oleogranulomatous mastitis-a rare entity.

Breast augmentation with the injection of a high-viscosity fluid has been practiced in the past, especially in Asia, resulting in most cases in different varieties of paraffinoma, alternatively known as oleogranulomatous mastitis, a complication of a 'foreign body' reaction type. We report our series of four consecutive cases of destructive paraffinomas that occurred in female patients who had had paraffin injection for cosmetic reasons. Complications due to paraffinoma reactions of breast tissue and skin, as well as progression of the disease and treatment of our patients, are presented here, together with a review of the relevant literature.

Mitoxantrone plus gemcitabine in pretreated patients with metastatic breast cancer.

Gemcitabine and mitoxantrone have both shown significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of this combination as second or third-line treatment in patients with metastatic breast cancer (MBC). Forty-six previously treated patients with MBC were enrolled from June 2000 to November 2002. Mean age was 56 years and ECOG performance status was < or =2. All patients received mitoxantrone 10 mg/m2, D8 and gemcitabine 1000 mg/m2, D1+8 every 21 days for 6 cycles. There were no complete responders. Objective response was observed in 12 patients (26%), 15 (33%) patients had stable disease, 15 (33%) had progressive disease and 4 (9%) were non-evaluable. At median follow-up of 27.8 months, overall survival was 13.3 months (range 0.6-33.8+) and the median time to disease progression (TTP) was 4.4 months (range 0.2-33.8). Toxicities (grade 3-4) were as follows: leukopenia 18 (39%), neutropenia 19 (41%), thrombocytopenia 4 (8.5%), anemia 6 (13%) and alopecia 1 (2%). Febrile neutropenia was recorded in 2 (4%) patients. There were no treatment related deaths. The authors conclude that the combination of mitoxantrone and gemcitabine is an effective regimen in pretreated patients with metastatic breast cancer. Toxicity was manageable.

Surgical management of nipple discharge.

PURPOSE: Nipple discharge is reported in 2.5-3% of women with breast carcinoma. Breast carcinoma is found in approximately 8% of surgically treated patients presenting with bloody nipple discharge (ND). METHODS: In the present study 110 women with ND as a presenting symptom were examined. The discharge was spontaneous in 76 and elicited in 11 patients. RESULTS: After surgical intervention benign breast disease was found in 85% of patients. Thirteen women (15%) were found to have malignancy and underwent additional surgery. Cytology of the discharge was positive or suspicious for malignancy in only seven out of 13 patients found to have in situ or invasive carcinoma. CONCLUSION: Women with spontaneous, single duct ND, especially when it is darkish or bloody, should have cytological examination of the fluid and mammography according to their age or additional clinical findings. Most of them will require a microdochectomy, as the possibility of finding a carcinoma among those women is between 10-15%. However, single duct papilloma is the most common cause of bloody discharge.

Wire localisation biopsy of non-palpable breast lesions: reasons for unsuccessful excision.

Surgical excision following needle-wire localization of nonpalpable, mammographically detected breast lesions is a very valuable diagnostic and therapeutic procedure. No further treatment is usually required after establishing an accurate histological benign diagnosis of indeterminate lesions on preoperative assessment. On the other hand, ductal carcinoma in-situ (DCIS) and early invasive cancer, properly excised, may sometimes require further management depending on specific histologic findings. An uncommon problem of this procedure is the failure to identify, localize or excise the breast lesion. In this review article, factors that contribute to the failed needle localization procedure are presented.

Impact of chemotherapy followed by aromatase inhibitors on bone health of women with ER-positive early breast cancer in real world clinical settings in Greece: Results of the POCHARBI trial conducted by the Hellenic Society of Breast Surgeons.

INTRODUCTION: The aim of this observational study was to assess the combined impact of chemotherapy (CT) and aromatase inhibitors (AI) therapy on bone mineral density (BMD) in postmenopausal women with estrogen receptor (ER)-positive early breast cancer. METHODS: Patients were treated with a third generation AI, either as adjuvant therapy (HT cohort, n = 166) or as subsequent endocrine therapy after initial treatment with chemotherapy (CT cohort, n = 124), and were followed up for a 12-month period. BMD was evaluated at lumbar spine (LS) and total hip (HP) before CT, before AI therapy and after 12 months of AI therapy. The primary study objective was changes in LS BMD between pre CT treatment and post 12 months AI therapy in the CT cohort. RESULTS: There were no statistically significant changes in LS BMD, either within CT or HT cohort. In the CT cohort, the mean LS BMD change was -0.72% (95% CI: -2.97%, +1.53%, p = 0.5526) between CT start and month 12 of AI therapy, while it was -0.19% (95% CI: -2.12%, +1.74%, p = 0.8309) and -0.59% (95% CI: -3.18%, +2.00%, p = 0.4759) between CT start and AI start and AI start and month 12 of AI therapy respectively. The mean change in LS BMD in the HT cohort (i.e. after 12 months of AI treatment) was +1.51% (95% CI: -0.96%, +3.98%, p = 0.7420). CONCLUSIONS: The results of this study indicate that, under routine clinical practice, most postmenopausal patients who receive CT before AI therapy do not experience debilitating BMD consequences during the first year of AI treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01298362.

Open surgical biopsy for nonpalpable breast lesions detected on screening mammography.

The aim of this retrospective clinical study was the analysis of histologic findings of nonpalpable breast lesions managed by open surgical biopsy. A series of 630 women underwent 664 preoperative localizations of nonpalpable, mammographically detected breast lesions during the last 10-year period. Indications for biopsy were (1) clustered microcalcifications, (2) solid mass, and (3) radiologic parenchymal distortion. The lesions were localized preoperatively using hook-wire methods, and all biopsies were performed under general anesthesia. Histopathology revealed carcinoma in 172 (25.9%) cases; noninvasive in 114 (66.3%) cases and infiltrating in 58 (33.7%) cases. The highest malignancy rate was found in cases with microcalcifications (112 carcinomas out of 323 cases, 34.7%). Lymph node invasion was present in 25% of patients with invasive cancers. The hook-wire localization of nonpalpable breast lesions is a simple, accurate and safe method for detection of early breast cancers. Frozen section is feasible and accurate in the majority of these lesions, and therefore, diagnostic and therapeutic one-step surgical procedures could be performed.