Reducing harms from treatment. Sixteen years of surgery of the axilla for screen-detected breast cancers in Italy.

OBJECTIVES: Available evidence on axillary surgery has accumulated dramatically in the last two decades in favor of less invasive care. The aim of this paper is to study 16-years trends in the surgical management of the axilla in a large population-based data set of screen-detected breast cancers in Italy and to document at what extent recommendations have been adopted in actual clinical care. MATERIAL AND METHODS: This is a retrospective cohort study documenting the surgical management of the axilla in primary breast cancer patients over time. We retrieved from the Italian database of screen-detected cancers 41213 cases diagnosed in women aged 50-69 between years 2000 and 2015 in twelve Italian Regions. RESULTS: In pN0 cases, an increasing trend (p < 0.001) in the number of patients who received sentinel lymph node biopsy (SLNB) as the only axillary staging procedure was observed. In pN + cases SLNB was the only staging procedure in an increasing number of patients (p < 0.001) especially since the publication of the ACOSOG-Z0011 paper. In ductal carcinoma in situ (DCIS) SLNB was more frequent in mastectomies and in high grade and large lesions. However, 45% of low grade, small DCIS over the whole time period had some form of axillary surgery. CONCLUSION: This large series of screen-detected cases documents a strong time trend in the direction of reducing axillary surgery and hence potential harms from treatment. The continuing practice of SLNB in low risk DCIS is of concern in an era of increasing awareness towards overdiagnosis and overtreatment.

Digital breast tomosynthesis (DBT): recommendations from the Italian College of Breast Radiologists (ICBR) by the Italian Society of Medical Radiology (SIRM) and the Italian Group for Mammography Screening (GISMa).

This position paper, issued by ICBR/SIRM and GISMa, summarizes the evidence on DBT and provides recommendations for its use. In the screening setting, DBT in adjunct to digital mammography (DM) increased detection rate by 0.5-2.7‰ and decreased false positives by 0.8-3.6% compared to DM alone in observational and double-testing experimental studies. The reduction in recall rate could be less prominent in those screening programs which already have low recall rates with DM. The increase in radiation exposure associated with DM/DBT protocols has been solved by the introduction of synthetic mammograms (sDM) reconstructed from DBT datasets. Thus, whenever possible, sDM/DBT should be preferred to DM/DBT. However, before introducing DBT as a routine screening tool for average-risk women, we should wait for the results of randomized controlled trials and for a statistically significant and clinically relevant reduction in the interval cancer rate, hopefully associated with a reduction in the advanced cancer rate. Otherwise, a potential for overdiagnosis and overtreatment cannot be excluded. Studies exploring this issue are ongoing. Screening of women at intermediate risk should follow the same recommendations, with particular protocols for women with previous BC history. In high-risk women, if mammography is performed as an adjunct to MRI or in the case of MRI contraindications, sDM/DBT protocols are suggested. Evidence exists in favor of DBT usage in women with clinical symptoms/signs and asymptomatic women with screen-detected findings recalled for work-up. The possibility to perform needle biopsy or localization under DBT guidance should be offered when DBT-only findings need characterization or surgery.

The Use of CYFRA 21-1 for the Detection of Breast Cancer Axillary Lymph Node Metastases in Needle Washouts of Fine-Needle Aspiration Biopsies.

BACKGROUND: In the preoperative setting of breast cancer, fine-needle aspiration biopsy (FNAB) guided by ultrasonography can be used to detect axillary lymph node metastases. The aim of the current study was to determine whether measurement in needle washouts of CYFRA 21-1, a soluble fragment of cytokeratin 19 (CK19), can improve the diagnosis of lymph node tumor deposits. MATERIALS AND METHODS: Our prospective study included 329 breast cancer patients eligible for a sentinel node procedure. Eighty-two patients had a ultrasonography-guided FNAB of an abnormal or suspicious axillary node and were included in the current analysis. Samples were processed with smears and cell-block histology; afterwards, needles were washed with saline solution, and the CYFRA 21-1 content in the washouts was measured. The cutoff value for positive samples that expressed CK19, as shown by their immunohistochemistry, was determined by a receiver operating characteristic curve. On the basis of this value, the specificity and the sensitivity, as well as the positive and negative predictive values, were then calculated using cytology results as a reference standard. RESULTS: Of the 82 axillary lymph nodes sampled, 61 were positive on cytology and were metastatic for breast cancer, as confirmed by surgery. The median CYFRA 21-1 concentration of positive samples was 88.94 ng/mL, whereas in the 21 negative nodes, its median concentration was 1.02 ng/mL (P<0.0001). A CYFRA 21-1 cutoff value of 1.98 ng/mL, obtained by the receiver operating characteristic curve, was able to clearly separate negative from positive samples and gave the test a sensitivity of 0.98 and a specificity of 1.00. Positive and negative predictive values were 1.00 and 0.95, respectively. CONCLUSIONS: The measurement of CYFRA 21-1 levels in needle washouts after axillary lymph node FNABs represents an accurate, sensitive, and highly predictive procedure in detecting metastatic deposits of breast cancer and is fit to complement cytology and CK19 immunohistochemistry as a diagnostic tool.

Recommendations for breast imaging follow-up of women with a previous history of breast cancer: position paper from the Italian Group for Mammography Screening (GISMa) and the Italian College of Breast Radiologists (ICBR) by SIRM.

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.

Lifestyle and breast cancer recurrences: the DIANA-5 trial.

AIMS AND BACKGROUND: The DIANA (Diet and Androgens)-5 study is a multi-institutional randomized controlled trial of the effectiveness of a diet based on Mediterranean and macrobiotic recipes and principles, associated with moderate physical activity, in reducing additional breast cancer events in women with early stage invasive breast cancer at high risk of recurrence because of metabolic or endocrine milieu. The intervention is expected to reduce serum insulin and sex hormones, which were associated with breast prognosis in previous studies. METHODS: Between 2008 and 2010, the study randomly assigned 1208 patients to an intensive diet and exercise intervention or to a comparison group, to be followed-up through 2015. General lifestyle recommendations for the prevention of cancer are given to both groups, and the intervention group is being offered a comprehensive lifestyle intervention, including cooking classes, conferences, common meals and exercise sessions. Adherence assessments occurred at baseline and at 12 months and are planned at 36 and 60 months. They include food frequency diaries, anthropometric measures, body fat distribution assessed with impedance scale, one week registration of physical activity with a multisensor arm-band monitor, metabolic and endocrine blood parameters. Outcome breast cancer events are assessed through self report at semi annual meetings or telephone interview and are validated through medical record verification. RESULTS: The randomized groups were comparable for age (51.8 years), proportion of ER-negative tumors (22%), axillary node metastasis (42%), reproductive variables, tobacco smoking, blood pressure, anthropometric measurements and hormonal and metabolic parameters. CONCLUSIONS: DIANA-5 has the potential to establish whether a Mediterranean-macrobiotic lifestyle may reduce breast cancer recurrences. We will assess evidence of effectiveness, first by comparing the incidence of additional breast cancer events (local or distant recurrence, second ipsilateral or contralateral cancer) in the intervention and in the control group, by an intention-to-treat analysis, and second by analyzing the incidence of breast cancer events in the total study population by compliance assessment score.