Treatment of invasive male breast cancer: a 40-year single-institution experience.

PURPOSE: We conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years. MATERIALS AND METHODS: We reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours. RESULTS: At a median follow-up of 8.9 [range, 0.6-20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003). CONCLUSIONS: In consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater pathological tumour size and positive nodal status as unfavourable features for survival in male breast cancer.

Concomitant adjuvant chemo-radiation therapy with anthracycline-based regimens in breast cancer: a single centre experience.

PURPOSE: This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline (AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the impact of treatment interruptions and the feasibility of this uncommon therapeutic approach. MATERIALS AND METHODS: From September 2002 to December 2007, 60 patients were treated at our Centre. The mean age at presentation was 48.5 (range 38-64) years. All patients underwent conservative surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46-52 Gy). AC-based regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). RESULTS: Concomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4 toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value. Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients. CONCLUSIONS: In our experience, concomitant chemotherapy did not emerge as a significant factor in radiotherapy interruption. Moreover, no severe cardiac events were recorded.

Dermo quiz: the illness and death of Anna Maria Lodovica de' Medici, Palatine Electress (1667-1743).

According to the unpublished documents, preserved in the Archives, the authors provide a possible explanation of the disease of the Anna Maria Lodovica de' Medici, the last descendent of the famous Florentine dynasty, suggesting that she could not have suffered from breast cancer, as it was claimed, but that she could have contracted syphilis. The opportunity to exhume her corpse in the frame of the Medici Project will supply evidence for this interpretation.

Postmastectomy radiotherapy in breast cancer adjuvant treatment.

Radiotherapy (RT) plays an important role in the management of locally advanced breast cancer (BC). Postmastectomy RT has been shown to significantly reduce the risk of loco-regional failure and to improve disease free survival in high-risk women with BC. Many trials have shown a significant benefit in local control, disease-free and overall survival with the addition of RT for patients with stage II and III breast cancer. New perspectives are evaluating multiple biological variables that nowadays should be considered in clinical oncology for the prescription of postmastectomy radiation therapy. Tailored randomized trials are now ongoing to clarify the "grey zone" represented by the intermediate-risk group of patients (1-3 lymph nodes involved). We reviewed the major studies offered by literature with emphasis on the principal debated issues.

Aesthetic results following breast cancer surgery: A prospective study on 6515 cases from ten Italian Senonetwork breast centers.

Breast cancer treatment has deeply changed in the last decades, since clinical and oncological cure cannot be achieved without patient's satisfaction in term of aesthetic outcomes. Several methods have been proposed to objectively assess these results. However, Italian breast centers have not yet agreed on measurable, reproducible and validated aesthetic outcome indicators to monitor their performance. METHODS: The study was designed and conducted by Senonetwork, a not-for-profit association of Italian breast centers. Ten breast centers were selected based on specific eligibility criteria. This multicentre observational prospective study recruited 6515 patients with diagnosis of in situ or invasive breast cancer who underwent breast surgery in the years 2013-2016. Thirteen indicators of aesthetic results and of related quality of care were analyzed. Data collection and analysis were conducted using a common study database. RESULTS: On average, seven out of ten centers were able to collect data on the proposed indicators with a proportion of missing values < 25%. By expert consensus based on study results, some seven indicators have been defined as "mandatory" while the remaining six have been defined as "recommended" because they require further refinement before they can be proposed for monitoring aesthetic outcomes or because there are doubts on the feasibility of data collection. The minimum standard is reached for 5 of 13 indicators. This finding and the wide range between centers reveal that there is ample room for improvement. CONCLUSIONS: From the present study useful measurable aesthetic parameters have emerged, leading to the definition of target objectives that breast centers can use for benchmarking and improvement of quality of care.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

EUSOMA accreditation of breast units.

EUSOMA (European Society of Mastology) is the organisation representing Breast Cancer Specialists in all disciplines, covering all aspects of breast cancer from risk and prevention, through diagnosis and treatment of the primary tumour, follow-up, treatment of recurrent and advanced disease, pathology, reconstruction, psychology and audit. EUSOMA Guidelines have been published on several aspects of breast cancer and are on service provision as well as giving clinical guidance and providing the basis for audit.

The management of elderly patients with T1-T2 breast cancer treated with or without radiotherapy.

AIM: The aim of the current study is to identify a subgroup of patients with breast cancer who have a low risk of local recurrence after conservative surgery in order to avoid radiotherapy treatment. METHODS: A group of 472 patients underwent conservative surgery without radiotherapy, and it was compared to a second group of 755 patients with similar characteristics, but who had received radiotherapy treatment (RT) after conservative surgery. RESULTS: Breast relapse's univariate analysis demonstrated statistical significance for the following factors: radiotherapy treatment, clinical stage, pathological stage, positive axillary nodes and tumour grading. Different results were obtained studying breast relapse. In the no-RT group breast relapse was 10.6% while in the irradiated group it was 3.4%. The breast relapse incidence decreases as the age of the patients increases especially over 75 years of age. CONCLUSIONS: In conclusion, there is clinical evidence of avoiding adjuvant radiotherapy for patients over 75 years with T1-T2 cancer treated with quadrantectomy with a clear excision margin.

Measurement of somatostatin receptor subtype 2 mRNA in breast cancer and corresponding normal tissue.

Somatostatin analogs are effective in inhibiting growth of human breast cancer cell lines. These antiproliferative effects are mediated by specific receptors located on cell membranes. The somatostatin receptor subtype 2 (sst2) is the principal mediator of somatostatin effects in normal and cancer cells, and its presence has already been demonstrated in breast cancer. The purpose of our study was to evaluate the clinical relevance of the expression of sst2 by quantifying its mRNA in a large group of infiltrating breast cancers and their corresponding normal tissues. The expression of sst2 mRNA was measured with quantitative real time RT-PCR in 169 breast cancers and in their corresponding unaffected tissues. We evaluated the association of sst2 expression with the commonest clinical-pathologic features of breast cancer. The correlation with a marker of cell proliferation (Ki-67) and with receptor concentration was also evaluated. In cancer tissues, we found that the absolute concentrations of sst2 mRNA were significantly higher in estrogen receptor (ER)-positive samples (P=0.002) as well as in lymph-node-negative cancers (P=0.04) (Student's t-test or one-way ANOVA). In addition, sst2 mRNA was significantly higher in breast cancers than in corresponding unaffected tissues (P=0.0002). However, when the clinical-pathologic parameters were considered, this gradient maintained its statistical significance only in tumors expressing positive prognostic markers, such as the presence of ER (P=0.0005) and progesterone receptors (PgR) (P=0005), and the lack of lymph-node involvement (P=0.0003). The same difference was also significant in postmenopausal women (P=0.001) and in T1 patients (P=0.001). In addition, sst2 mRNA expression was significantly higher (P=0.008) in low-proliferating breast cancers. Finally, we found that the quantitative expression of sst2 mRNA was directly related to the PgR concentration in breast cancer tissues (P<0.001). Our data seem to indicate that an upregulation of sst2 gene expression is a common feature of breast cancers which, on the basis of conventional predictive parameters, are expected to have a better prognosis. Featuring a possible role of somatostatin analogs in combined endocrine therapies for breast cancer, our results seem to confirm that the sst2 status of the tumor should be previously investigated.

Non-palpable lesions of the breast detected by mammography--review of 1182 consecutive histologically confirmed cases.

We report on 1182 consecutive histologically confirmed non-palpable breast lesions detected by mammography (infiltrating carcinoma 427, in situ carcinoma 121, benign 634). The proportion of cancer cases varied according to age (< 50 years = 33%; 50-59 years = 46%; > 59 years = 63%), mammographic pattern (regular opacities = 8%, parenchymal distortions = 20%, isolated calcifications = 42%, irregular opacities = 62%, stellate opacities = 73%), and calendar period (1970-1985 = 29%, 1986-1989 = 56%; 1990-1992 = 69%). A sharp decrease of the benign/malignant biopsy ratio was evident after routine fine-needle aspiration cytology (sonography-guided or stereotaxic) was introduced in 1986. The independent significant association of cancer frequency to age, calendar period and mammographic pattern was confirmed by multivariate analysis. A significant trend over time in favour of conservative surgery was also observed for cancer cases (1970-1979 = 6%, 1980-1985 = 41%, 1986-1992 = 83%). Among invasive cancers, node involvement was observed in 11.5% of cases, being associated with tumour size (pT1a = 0%, pT1b = 7%, pT1c = 13%, pT2a = 33%). Five-, ten- and fifteen-year overall survivals of invasive cancers were 98.1, 95.7 and 87.3%, respectively.

Monitoring surgical treatment of screen-detected breast lesions in Italy.

The object of this study was to assess quality of care and adherence to treatment guidelines of screen-detected lesions in Italy using a new audit system. Data on screen-detected cases surgically treated in 1997 were collected using a system (QT 2.3) developed within the Italian Group for Planning and Evaluating Mammographic Screening Programmes (GISMa) and the European Breast Cancer Screening Network. Results of 18 performance parameters were considered compared with the reference standards. In 1997, 515 lesions (335 invasive, 60 in situ and 120 benign) in 496 patients were collected from 14 departments in the Central and Northern area of Italy. The 18 indicators were analysed and grouped according to six quality objectives. Some results were good and others were excellent, such as intraoperative identification, breast conservation surgery, adequate axillary procedures and completeness of pathology reports, but most of them failed: waiting times, preoperative diagnosis, employment of frozen section on small lesions and avoiding axillary procedures in ductal carcinoma-in-situ. This work is a first attempt in Italy to evaluate and uniform the criteria adopted for quality control of breast cancer treatment, using a standardised system. Some results are good or excellent, the overall level of compliance with quality indicators is not satisfactory and corrective actions should be undertaken for a number of issues. A continuous monitoring should be performed and appropriate action taken in order to verify the effectiveness of the corrective actions and to provide screen-detected patients with the best quality of care.

Intraductal breast cancer: review of 183 consecutive cases.

The aim was to review a series of 183 intraductal breast cancer to define the diagnostic features and therapeutic outcome. Patients' average age was 54 years. Diagnostic procedures employed were clinical examination, mammography in 173 cases and fine-needle aspiration cytology in 98 cases. The sensitivity of clinical examination was 0.61, of mammography 0.74, of fine needle aspiration cytology 0.70. The sensitivity of clinical examination and mammography associated was 0.93. The surgical options adopted were: conservative surgery 80 cases, mastectomy 103 cases. Conservative surgery was followed by breast irradiation in 34 cases. Axillary dissection was performed in 122. 97 cases have been reviewed histologically. 60% of ductal carcinoma in situ (DCIS) were multifocal and 22% multicentric. Local recurrence, all infiltrating, occurred in the same breast after conservative surgery in 8 cases, 3 of which had received postoperative radiotherapy, and in 3 patients after mastectomy. Contralateral breast cancer was recorded in 13 cases, being synchronous in 4 (infiltrating in 3, DCIS in 1) and metachronous in 8 (all infiltrating). 3 patients died of breast cancer. The present series confirms the risk of ipsilateral cancer recurrence after conservative surgery but there are no significant differences relating to mammographic pattern, size, histological type, margin involvement and radiotherapy.

Comparison of the surgical procedures for breast conserving treatment of early breast cancer in seven EORTC centres.

The aim of this study was to develop a standardised surgical report for breast-conserving procedures, supporting the systematic documentation of the different aspects of the surgery. The surgical procedure for tumourectomy and axillary clearance was translated into a series of steps that could be quantitatively documented. This description was submitted twice to a group of surgeons from different departments to ensure that all steps that are considered to have relevance for outcome were included and that no superfluous data were collected. After two corrective phases, a first test format was developed. Between February 1993 and May 1994, seven surgical departments, participating in EORTC trials, completed this questionnaire for a number of their patients. The data collected related to general information on the department, the tumour excision itself, the axillary dissection and, in a later phase, on pathology. 269 questionnaires (264 tumour excisions, 259 axillary dissections and 189 pathology reports) were collected and analysed. Even though the participating departments were involved in a single trial on breast-conserving surgery and had previously developed regular contacts about the practical aspects of treatment, many differences were detected. In general, variations were found in the waiting time between treatment prescription and execution, experience of the surgeon, duration of the procedure, and the use of prophylactic antibiotics. Also, in the practical execution of the procedure, major variations in the type of incision, width of tumour excision, closure of the breast tissue and skin, the use of frozen sections and the extent of the axillary dissection were found. The most relevant differences and their possible consequences are discussed. It has been proven possible and feasible to document quantitatively a surgical procedure. The fact that within a group of surgeons participating in the same clinical trials, many differences in the surgical techniques are observed, stresses the need to reach a consensus on a stricter set of guidelines for breast-conserving procedures and their documentation, especially when conducting clinical trials.

Patterns of axillary metastases in breast cancer.

Thirty-seven (4.1%) cases of nodal metastases skipping the first level are reported in a consecutive series of 912 breast cancer axillary dissections including 392 N+ cases. First level nodes examination is sufficiently accurate in assessing the quality of nodal status (negative or positive) but not the extent of nodal involvement (number of involved nodes).

Prognostic significance of estrogen receptor determination in primary breast cancer.

The authors report on 767 consecutive primary Stage I-II breast cancer cases followed-up from 3 to 8 years. The estrogen receptor (ER) content was determined in all cases and did not influence the treatment choice. A correlation was attempted between ER and menstrual or pathological nodal status (N) or the 5-year disease-free survival (DFS). ER was correlated with menopausal status ER+ cases being more frequent in postmenopausal patients, whereas no correlation was observed between ER and nodal status. In absence of nodal involvement (N-) the prognosis was not influenced by the ER status. A significantly better DFS was evident for ER+ respect to ER- patients in the N+ series but such a correlation is questionable as the adjuvant treatment (hormone or chemotherapy) given to such patients may have influenced the DFS according to the ER status. According to the present study, ER determination should not be used as a discriminant in the performance of adjuvant postoperative treatment based on a prognostic judgment.

Cancer reoccurrence in the conserved breast - diagnostic features in a consecutive series of 102 cases.

Diagnostic features of 102 consecutive cases of cancer reoccurrence in the conserved breast are reported. The sensitivity of palpation, mammography, cytology or ultrasonography was 75.5%, 58.7%, 77.4% and 77.8%, respectively. Mammography failures were not due to natural breast density and could probably be explained by the masking effect of surgical scar and distortion. Most failures at cytology were due to inadequate sampling. Palpation should always be associated with mammography in the follow-up of the conserved breast. Aspiration cytology should.be performed incase of any abnormality seen at palpation or mammography.

Accuracy and reliability of frozen section diagnosis in a series of 672 nonpalpable breast lesions.

Frozen section (FS) diagnosis was routinely performed in a large series of nonpalpable breast lesions from 1977 through 1991. The original FS diagnoses of 672 patients were classified in four categories (1 = benign lesion, 2 = in situ carcinoma, 3 = invasive carcinoma, 4 = deferred diagnosis) and compared with the diagnoses obtained at review of the permanent paraffin sections to estimate the accuracy of FS. A review of the mammographic pattern of the lesion was also performed. Frozen section diagnostic conclusion was deferred to permanent paraffin sections in only 22 cases (3.3%). Benign or malignant (grouping in situ and invasive carcinomas) FS diagnoses were accurate in 623 of 650 cases (95.8%). Overall, the prevalence of malignant lesions was 44.8% with a benign/malignant ratio of 1.2. The diagnosis was modified on the basis of permanent sections in 27 cases (4.2%) with three false positives and 24 false negatives. Sensitivity and specificity of FS diagnoses were 91.7 and 99.2%, respectively. When the comparison between FS and histologic diagnoses was analyzed according to the mammographic pattern, sensitivity among patients with microcalcifications as the only alteration was lower (88.8%) than among patients with opacities (94.9%). On the basis of these results, FS is to be considered a feasible and reliable diagnostic procedure in nonpalpable breast lesions, particularly in cases excised because of a mammographic opacity that is identifiable on gross examination of the surgical specimen.

Alkaline phosphatases and steroid receptors in human breast cancer.

Estrogen receptors (ER), progesterone receptors (PR) and alkaline phosphatases (AP) were measured in 150 tumors from patients who underwent mastectomy for primary breast cancer. The percentage of ER positive samples was inversely related to the AP activity ranging from 88.9% in low activity samples (less than 30 U/mg prot.) down to 30.6% in the high activity ones (greater than 400 U/mg prot.). When considering only ER positive samples, the ER content was inversely related to the AP activity. This could not be demonstrated for PR. Therefore, the authors suggest the hypothesis that in human breast cancer, the AP may play a role in the dephosphorylation of the ER molecule and in the consequent modulation of its binding capability.

Phyllodes tumor of the breast: a multicenter series of 59 cases. Coordinating Center and Writing Committee of FONCAM (National Task Force for Breast Cancer), Italy.

A series of 59 phyllodes tumors of the breast was retrospectively reviewed (average follow-up = 3.9 years). Clinical features (age, size of tumor) and diagnostic tests (palpation, mammography, sonography and cytology) were found to be inaccurate in predicting benign (n = 22), borderline (n = 12) or malignant (n = 25) histological type. Limited surgery was associated with a relatively high proportion of local recurrence (enucleation/enucleoresection = 3/5, wide resection = 12/30) compared with mastectomy (2/24). No significant association was observed between the probability of local recurrence and patient's age, histological type or lesion size. Although the study confirms that limited surgery may cure phyllodes tumor, careful follow-up of all patients is needed, since no reliable risk factors for recurrence are available. In malignant cases, axillary node involvement was nil and distant metastases were infrequently observed (3/25). Axillary dissection and search for asymptomatic metastases is not recommended.

Principles and guidelines for surgeons--management of symptomatic breast cancer. European Society of Surgical Oncology.

The European Society of Surgical Oncology is actively involved in the promotion of a high standard of surgical oncology throughout Europe. Such an ambition involves recognition of Centres of Excellence in the management of cancer patients throughout Europe. These centres have a multi-disciplinary system involved in the total care of patients with cancer and are concerned with the delivery of care to the highest available standards. It is accepted that not all patients with cancer can, nor should, necessarily be treated in such highly specialized centres. Yet all cancer patients should be guaranteed a high standard of care. High surgical standards can be ensured if surgeons treating cancer are trained in specialist centres and, when in independent practice, follow established guidelines or protocols of treatment. In common with many national surgical oncology societies, the European Society of Surgical Oncology is in the process of establishing good practice guidelines in the treatment of solid tumours. This document on the management of symptomatic breast cancer is the first of a series of guidelines to be proposed by ESSO. It draws heavily on excellent documents already in existence from the British Association of Surgical Oncology and from the Danish Breast Cancer Co-Operative Group. It is hoped that this document will be sufficiently clear and purposeful to be of help to the individual surgeon and yet sufficiently flexible to allow it to be adopted in the different medical systems throughout Europe.