The requirements of a specialist breast centre.

This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.

Quality indicators in breast cancer care: An update from the EUSOMA working group.

In 2010, EUSOMA published a position paper, describing a set of benchmark quality indicators (QIs) that could be adopted by breast centres to allow standardised auditing and quality assurance and to establish an agreed minimum standard of care. Towards the end of 2014, EUSOMA decided to update the paper on QIs to consider and incorporate new scientific knowledge in the field. Several new QIs have been included to address the need for improved follow-up care of patients following primary treatments. With regard to the management of elderly patients, considering the complexity, the expert group decided that, for some specific quality indicators, if centres fail to meet the minimum standard, older patients will be excluded from analysis, provided that reasons for non-adherence to the QI are specified in the clinical chart and are identified at the review of the clinical records. In this way, high standards are promoted, but centres are able to identify and account for the effect of non-standard treatment in the elderly. In the paper, there is no QI for outcome measurements, such as relapse rate or overall survival. However, it is hoped that this will be developed in time as the databases mature and user experience increases. All breast centres are required to record outcome data as accurately and comprehensively as possible to allow this to occur. In the paper, different initiatives undertaken at international and national level to audit quality of care through a set of QIs have been mentioned.

Fluctuating mastectomy rates across time and geography.

In 2009, 2 single-institution studies from the United States reported increasing mastectomy rates during the last decade. We have recently reported unilateral mastectomy trends from a European database and demonstrated a significant trend of decreasing mastectomy rates from 38.1 % in 2005 to 13.1 % in 2010. A recent study from the SEER registry in the United States confirmed a previously reported decrease in mastectomy rates from 40.1 % in year 2000 to 35.6 % in 2005, but showed a statistically significant increase in mastectomy rates up to 38.4 % in 2008. This report provides evidence that mastectomy trends may be in opposite directions in different geographical areas. The sharpest increase in mastectomy rates across all ages in the recent SEER study occurs right after year 2005, which interestingly corresponds with the time of publication of the meta-analysis by the EBCTCG that highlighted the importance of local control in breast cancer. The coincident timing raises the question of whether this evidence may have indirectly triggered an increase in mastectomy rates in the United States that would partially explain the observed trend, and more importantly, of whether an increase would be justified on this basis. Multiple factors influence the proportion between mastectomy and breast conservation, so it may be unreasonable to think of an optimal cutoff. There is not necessarily a right or wrong direction for mastectomy trends, but aiming to determine explanations for these differences may help provide a clearer insight of the decision-making process involved in the surgical management of breast cancer.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results of quality indicators on screen-detected lesions in Italy for 2006 and preliminary results for 2007.

Within this survey, conducted by the Italian Breast Screening Network (Gruppo Italiano per lo Screening Mammografico, GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2006, results showed overall good diagnosis and treatment quality and an improving trend over time. Critical issues were identified in waiting times, compliance with recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis reached the acceptable target, but there is a large variation between Regions and programmes. The sentinel lymph node technique (SLN) was performed on the axilla in more than 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN in ductal carcinoma in situ deserves further investigation. The detailed results have been distributed to regional and local screening programmes, also by means of an online database, in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making audit effective in producing quality improvement with a shortening of waiting times.

Physical activity and mammographic breast density in a Mediterranean population: the EPIC Florence longitudinal study.

A protective effect of physical activity (PA) on breast cancer (BC) risk has been suggested. Few studies have examined the influence of PA on mammographic breast density (MBD), a strong risk factor for BC. In a prospective study in Florence, Italy, we identified 2,000 healthy women with a mammogram taken 5 years after enrollment. Individual mammograms were retrieved (83%) and MBD assessed according to Wolfe's classification. Detailed information on PA at work and during leisure time, reproductive history, lifestyle and anthropometric measurements at enrollment were available for 1,666 women. Information on hormone replacement therapy (HRT) was also obtained at mammogram. Women with high-MBD (P2 + DY Wolfe's patterns) were compared with women with low-MBD (N1 + P1) by multivariate logistic models. Overall, high-MBD was inversely associated with increasing levels of leisure time PA (p for trend = 0.04) and among peri-/postmenopausal women, also with increasing levels of recreational activities (p for trend = 0.02). An interaction between PA and HRT emerged, with a stronger inverse association of highest level of recreational activity with MBD among HRT nonusers (p for interaction = 0.02). A modifying effect by body mass index (BMI) was evident among 1,025 peri-/postmenopausal women who did not use HRT at the time of mammogram, with a stronger inverse association between recreational PA and MBD in the highest BMI tertile (OR = 0.34; 95% CI 0.20-0.57; p for interaction = 0.03). This large study carried out in Mediterranean women suggests that leisure time PA may play a role in modulating MBD, particularly in overweight/obese peri-/postmenopausal women.

Audit system on quality of breast cancer diagnosis and treatment (QT): results of quality indicators on screen-detected lesions in Italy in 2005 and preliminary results for 2006.

Within this survey, conducted by the Italian Group of Mammography Screening (GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2005, results showed overall good diagnosis and treatment quality, and an improving trend over time. Critical issues were identified in waiting times, compliance with the recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis has reached the acceptable target, but room for improvement still exists. The sentinel lymph node technique (SLN) was performed on the axilla in more than 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

Does computer-aided detection (CAD) contribute to the performance of digital mammography in a self-referred population?

BACKGROUND: Recent evidence suggests that computer-aided detection (CAD) may have a negative impact on the interpretation of mammography-this necessitates timely evaluation of CAD in practice. We report a retrospective study of the incremental effect of CAD on the accuracy of full-field digital mammography (DM) as applied prospectively in breast assessment. METHODS: Subjects were all consecutive women attending a self-referral breast centre in Florence between September 2005 and January 2007 (N = 3,425). DM was reported without, then with, CAD according to a standard protocol; all mammograms recalled on the basis of either the radiologist's reading alone, or the radiologist's reading after viewing CAD, were recalled to assessment. RESULTS: Overall recall rate (RR) was 13.1% and 107 cancers were diagnosed (90 invasive cancers, 8 DCIS, 9 malignant on cytology). The use of CAD allowed the additional detection of 5 cancers (three invasive cancers, one DCIS, one malignant on cytology) and caused one additional benign surgical biopsy, with a relative RR of 4.9%, and an incremental RR of 1.17%. The cancer detection rate (CDR) of DM interpreted with the use of CAD was 3.12% and did not significantly differ from the CDR of 2.9% based on DM without CAD (chi(2) = 3.2, P = 0.07). CONCLUSION: While the increase in CDR with the use of CAD only approached statistical significance, representing modest gains in absolute terms, the incremental number of cancers detected justifies the incremental recall and benign surgical biopsy attributable to CAD use. In our clinical setting, these data suggest more benefit than harm in using CAD with DM, and we will continue the use of CAD with ongoing monitoring of patient outcomes.

Audit system on quality of breast cancer diagnosis and treatment (QT): results from the survey on screen-detected lesions in Italy, 2004.

Within this survey, conducted by the Italian Group for Mammography Screening (GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2004, overall results show a good diagnosis and treatment quality and an improving trend over time. Critical issues have been identified in waiting times, compliance to the recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis has reached an acceptable level, but room for improvement still exists. The sentinel lymph node technique (SLN) was performed on the axilla in almost 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed to local and regional screening programmes in order to enable multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volumes would provide the best setting for effective audits leading to quality improvement.

Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis.

BACKGROUND: A reduced activity of methylenetetrahydrofolate reductase (MTHFR) due to frequent C677T polymorphism affects DNA synthesis, repair and methylation and may be implicated in breast cancer risk. METHODS: We conducted a nested case-control study within a phase III prevention trial of tamoxifen. After a median follow-up of 81.2 months, 79 of the 5,408 hysterectomised women aged 35-70 years, who had received either tamoxifen 20 mg/day or placebo for 5 years, developed breast cancer. A total of 46 breast cancer cases and 80 unaffected controls matched to treatment allocation, years from randomization (+/-2 years) and age at randomization (+/-5 years), underwent genotyping for MTHFR C677T polymorphism using real time PCR. RESULTS: The MTHFR 677 genotype frequencies for CC, CT, TT in breast cancer cases were 30%, 44% and 26%, respectively, and 35%, 51%, 14% in controls. We observed a borderline significant odds ratio of 2.51 (95% CI, 0.96-6.55) of breast cancer in subjects with 677TT genotype, with no further association after stratifying for age and treatment group. A meta-analysis of 18 studies, including our own, showed an increased risk of breast cancer in premenopausal women with 677TT genotype, with an odds ratio of 1.42 (95% CI, 1.02-1.98). CONCLUSIONS: Our study lends support to a positive association between the MTHFR variant homozygous allele 677TT and breast cancer risk. Additional studies are warranted to provide further insight into the role of folate metabolism deficiency and breast cancer.

Importance of comparison of current and prior mammograms in breast cancer screening.

PURPOSE: To retrospectively determine the influence of comparing current mammograms with prior mammograms on breast cancer detection in screening and to investigate a protocol in which prior mammograms are viewed only when necessary. MATERIALS AND METHODS: Institutional review board approval was not required. Participants gave written informed consent. Twelve experienced screening radiologists read 160 soft-copy screening mammograms twice, once with and once without prior mammograms. Eighty mammograms were obtained in women in whom breast cancer was diagnosed later; the other 80 mammograms had been reported as normal or benign. All cancers were visible in retrospect. Readers located potential abnormalities, estimated likelihood of malignancy for each finding, and indicated whether prior mammograms were considered necessary. The effect of prior mammograms on detection was determined by computing the mean lesion localized fraction in a range of low fractions of nonlesion locations corresponding to operating points in screening. Scores for both reading sessions were combined to assess the effect of making prior mammograms available only when requested. Data were analyzed by comparing the number of localized lesions between the two reading conditions with a paired two-tailed Student t test and applying a linear mixed model to test differences in average mean lesion localized fraction between reading conditions. P values less than .05 indicated statistical significance. RESULTS: Without prior mammograms, significantly more annotations were made. When only positive cases were considered, no difference was observed. Reading performance was significantly better when prior screening mammograms were available. At fixed lesion localized fraction, nonlesion localized fraction was reduced by 44% (P<.001) on average when prior mammograms were read. Performance was also increased for combined reading mode (ie, when prior mammograms were available on request only). However, this increase was smaller than that when prior mammograms were always available. Prior mammograms were requested in 24%-33% of all cases and were requested more often in positive cases. CONCLUSION: Comparison with prior mammograms significantly improves overall performance and can reduce referrals due to nonlesion locations. Limiting the availability of prior mammograms to cases selected by the reader reduces the beneficial effect of prior mammograms.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results from the survey on screen-detected lesions in Italy, 2003-2004.

Within the Italian Breast Screening Network, individual data are collected yearly on about 50% of all screen-detected operated lesions. In 2003 results showed a good overall quality of diagnosis and treatment, and an improving trend over time. Critical issues were identified in the number of cancers diagnosed pre-operatively, which is still below standards, and in the waiting times for surgery. Compliance with recommendations as to not performing frozen section on small lesions and unnecessary axillary dissection for ductal carcinoma in situ still have not reached the target. The sentinel lymph node technique was performed on the axilla in more than 60% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. Preliminary data for 2004 show further progress towards better quality, particularly in pre-operative diagnosis and in the avoidance of frozen section. The detailed results of this survey have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

Role of ultrasound-guided fine needle cytology of axillary lymph nodes in breast carcinoma staging.

PURPOSE: To evaluate the efficacy of cytology on axillary lymph node ultrasound-guided aspiration biopsy in the reduction of inappropriate surgery, such as the sentinel node (SN) procedure if positive, or axillary dissection if negative. MATERIALS AND METHODS: Cytology was performed on 159 consecutive cases, on the ultrasonographically most suspicious lymph node. Lymph node histology was used as a reference standard to determine accuracy. Four different scenarios were simulated: routine axillary ultrasonography with cytology of the lymph nodes visible at ultrasonography (A), or of only the lymph nodes suspicious at ultrasonography (B), with ultrasonography limited to clinically negative axillae and cytology of the lymph nodes visible at ultrasonography (C), or only of the lymph nodes suspicious at ultrasonography only (D). RESULTS: Cytologic sensitivity was 58.6%, specificity 100%. Immediate axillary dissection only in the case of positive cytology would have avoided 6/6 inappropriate axillary dissections and 5/34 (14.7%) inappropriate SN, compared to routine practice (immediate dissection for palpable adenopathy, SN in the remaining cases). Each of the simulated scenarios saved inappropriate surgical procedures (A: 6 dissections, 5 SNs; B: 6 dissections, 3 SNs; C: 13 SNs; D: 11 SNs) at no expense (A and B) or limited expense (C: Euro 348, D: Euro 232 for each inappropriate surgical procedure saved). CONCLUSIONS: Axillary lymph node cytology can save axillary dissections or sentinel node procedures and is recommended as routine practice. Routine axillary ultrasonography, with cytology of sonographically visible lymph nodes, followed by immediate axillary dissection only in case of positive cytology proved to be the best approach in terms of cost-benefit ratio.

Comparison of two commercial systems for computer-assisted detection (CAD) as an aid to interpreting screening mammograms.

PURPOSE: To compare the diagnostic accuracy of two commercial CAD systems (CADx and R2) and their impact as an aid to conventional reading of screening mammograms. MATERIALS AND METHODS: The image set considered consisted of 120 mammograms, 89 confirmed negative and 31 with subsequent interval cancers (11 classified as false negatives (FN), 20 as "minimal signs" (MS)). The set was digitised and processed with CAD, and printouts obtained of the mammograms with indications of the areas warranting review. Six expert radiologists read the mammograms three times, once using conventional reading and twice using CAD reading with CADx and R2, respectively. The two CAD systems were compared in terms of diagnostic accuracy of the marks and the impact of CAD reading compared to conventional reading and to the use of independent second reading simulated by combining pairs of single conventional readings. RESULTS: R2 highlighted more calcifications (218 vs 132, +65%) and CADx highlighted more masses (208 vs 105, +98%). CADx and R2 marked 15 and 17 out of 31 cancers, respectively (sensitivity 48.3% vs 54.8%, chi squared=6.4, p=0.79), 10 and 6 out of 11 FN (90.9% vs 54.5%, chi squared=2.0, p=0.15), respectively, and 5 and 11 out of 20 MS (25.0% vs 55.0%, chi squared=2.6, p=0.10), respectively. As for specificity, the false positive markings for masses were on average (per case) 1.60 for CADx and 0.75 for R2, those for calcifications were 1.08 for CADx and 1.77 for R2 and the total false positive markings were 2.68 for CADx and 2.52 for R2. CADx and R2 marked 73 and 63 of 89 negative controls (specificity = 0.18 vs 0.29, chi squared=2.52, p=0.11), respectively. All the radiologists showed greater sensitivity with CAD reading compared to conventional reading. On average, sensitivity with conventional reading was 58.6% (109/186), as against 70.9% (132/186) for CADx or R2 (chi squared=5.71, p=0.016). Sensitivity for FN cases was 71.2% (47/66) with conventional reading, 84.8% (56/66) with CADx (chi squared=2.82, p=0.09) and 80.3% (53/66) for R2 (chi squared=1.03, p=0.30) (CADx vs R2, chi squared=0.21, p=0.64). Sensitivity for MS cases was 51.6% (62/120) for conventional reading, 63.3% (76/120) for CADx (chi squared=2.88, p=0.08) and 65.8% (79/120) for R2 (chi squared=4.40, p=0.03) (CADx vs R2, chi squared=0.07, p=0.78). The recall rates were 18.1% (97/534) for conventional reading, 29.7% (159/534) for CADx (chi squared=5.72, p=0.01) and 24.3% (130/534) for R2 (chi squared=10.11, p=10-5) (CADx vs R2, chi squared=3.71, p=0.05). Double reading was significantly more sensitive than conventional reading (chi squared=29.6, p=10-6), CADx (chi squared=5.33, p=0.02) and R2 (chi squared=5.33, p=0.02). The recall rate for double reading was significantly higher than for conventional reading (chi squared=21.5, p=10-6) whereas no significant difference was detected when compared to CADx (chi squared=0.16, p=0.68) or R2 (chi squared=3.4, p=0.06). CONCLUSIONS: Despite using different algorithms, the two CAD systems exhibit comparable levels of diagnostic accuracy and a similar positive impact on sensitivity when used as an aid to conventional reading. Single reading with either CAD system is as specific but not as sensitive to double independent reading: its use as an alternative to double reading cannot be recommended and should be investigated further by means of controlled prospective studies.

Comparison of standard reading and computer aided diagnosis (CAD) on a proficiency test of screening mammography.

PURPOSE: To evaluate the role of computer aided diagnosis (CAD) to improve screening mammograms interpretation. MATERIALS AND METHODS: Six radiologists underwent a screening mammography proficiency test first by conventional, then by CAD assisted reading. Sensitivity and recall rate at conventional and CAD reading were compared. Independent conventional double reading was simulated (15 pair combinations) and compared to single CAD reading. RESULTS: CAD marked 31 of 32 cancers (case-based sensitivity=96.8%). On a film and lesion basis, CAD identified 31 of 32 (96.8%) malignant calcifications and 29 of 42 (69.0%) malignant opacities, the only cancer not identified by CAD being depicted as an isolated opacity. CAD marked 348 areas (153 microcalcifications and 195 opacities) in 88 of 108 non cancer cases, with a case-based specificity of 18.5% (20/108). Considering all six readings, cancer was identified in 164 or 174 of 192 readings (85.4 vs 90.6%, c2 2.03, df=1, p=0.15) and recalls of non-cancer cases were 108 or 159 of 648 readings (16.6 vs 24.5%, c2 11.7, df=1, p<0.001) at conventional or CAD reading, respectively. CAD reading (average of 6 readings, 192 cancer, 648 non-cancer readings) was slightly, non significantly less sensitive (sensitivity 90.6 vs 92.9%, c2 0.73, df=1, p=0.39) and slightly, but not significantly more specific (recall rate 24.5 vs 26.1%, c2 0.56, df=1, p=0.45) as compared to simulated independent double reading (average of 15 combinations, 480 cancer, 1620 non-cancer readings). CONCLUSION: CAD seems to allow for a limited absolute increase (+5.2%) in sensitivity and for a limited absolute increase (+7.9%) in recall rate, the latter difference only reaching statistical significance. CAD reading showed no significant difference in diagnostic accuracy as compared to conventional (simulated) double reading, although further studies are needed to confirm it as possible alternative to double reading in the current screening practice.

Does family history influence survival in breast cancer cases?

A few studies have suggested a relatively better prognosis for breast cancer (BC) cases reporting a positive family history (FH). We aimed at comparing the survival of patients according to FH in a large hospital-based series of 1,278 BC cases. Information on FH for BC was obtained at diagnosis by interview. All cases reporting a first- or second-degree FH for breast carcinoma were compared with cases without FH. Overall survival was estimated using a product-limit method. Hazard ratios (HRs) and the corresponding 95% confidence intervals (95% CIs), adjusted for confounding factors, were computed using proportional hazard models. Overall, 240 (18.8%) cases reporting, at diagnosis, a positive FH (156 with at least 1 first-degree relative and 84 with at least 1 second-degree relative) were compared with 1,038 patients without FH for BC. No significant differences were found in terms of distribution of age at diagnosis, tumor stage, nodal involvement, receptor status and histology. Cumulative survival rates at 5 years for cases without FH and with first-degree and second-degree FH for BC were 79.8 (95% CI 77.0-83.0), 78.6 (95% CI 70.0-88.0) and 80.2 (95% CI 68.0-92.0), respectively (log-rank test, chi(2) (2) = 0.02, p = 1.0). After adjustment for age, pathologic size and nodal involvement, the HR among cases of invasive cancer with a first-degree FH of BC was 0.91 (95% CI 0.55-1.48); however, the HR for cases with second-degree FH was 1.18 (95% CI 0.62-2.25) compared to cases without FH. Our study, based on a large series of consecutive invasive BC cases, did not find any significant survival differences associated with a positive FH for breast carcinoma, suggesting the existence of a large heterogeneity among BC cases with FH.