Outcomes after breast-conserving surgery or mastectomy in patients with triple-negative breast cancer: meta-analysis.

BACKGROUND: In patients with triple-negative breast cancer (TNBC), oncological and survival outcomes based on locoregional treatment are poorly understood. In particular, the safety of breast-conserving surgery (BCS) for TNBC has been questioned. METHODS: A meta-analysis was performed to evaluate locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) rates in patients with TNBC who had breast-conserving surgery versus mastectomy. Estimates were pooled in random-effects analysis. The effect of study-level co-variables was assessed by univariable metaregression. RESULTS: Fourteen studies, including 19 819 patients operated for TNBC met the inclusion criteria; 9828 patients (49.6 per cent) underwent BCS and 9991 (50.4 per cent) had a mastectomy. Patients with smaller tumours were more likely to be selected for BCS (pooled odds ratio (OR) for T1 tumours 1.95, 95 per cent c.i. 1.64 to 2.32; P < 0.001). The pooled OR for LRR was 0.64 (0.48 to 0.85; P = 0.002), indicating a statistically significantly lower odds of LRR among women who had BCS relative to mastectomy. The pooled OR for DM was 0.70 (0.53 to 0.94; P = 0.02), indicating a lower odds of DM among women who had BCS; however, this difference diminished with increasing study-level age and follow-up time. A pooled hazard ratio of 0.78 (0.69 to 0.89; P < 0.001) showed a significantly lower hazard for all-cause mortality among women undergoing BCS versus mastectomy. CONCLUSION: These results should be interpreted cautiously owing to likely differences in selection for BCS or mastectomy in the included studies. Patients with TNBC selected for BCS do not, however, have a worse prognosis than those treated with mastectomy, and breast conservation can be offered when feasible clinically.

Intraoperative digital breast tomosynthesis using a dedicated device is more accurate than standard intraoperative mammography for identifying positive margins.

AIM: To compare a standard intra-operative mammography (IM) device with digital breast tomosynthesis using a dedicated device (Mozart system) in the evaluation of surgical margins at first excision. MATERIALS AND METHODS: The study received institutional review board approval and written informed consent was obtained from participants. From January 2018 to December 2018, a prospective analysis of the images of IM device and intra-operative digital breast tomosynthesis with a dedicated device (Mozart system) in n=89 breast cancer patients (average patients age: 58 years, age range: 35-76 years) was undertaken. Images were evaluated by two expert breast radiologists independently of each other and blinded to each other's interpretation, who indicated the positive cases requiring surgical re-excision intra-operatively. RESULTS: Mean cancer size was 12.5±4.5 mm. Radiological signs of the lesions were microcalcifications (n=71), nodules (n=10), and architectural distortions (n=8). A total of 20/89 (17%) patients underwent intra-operative re-excision for positive margins. Intra-operative digital breast tomosynthesis with a dedicated device and IM showed discrepancies in 15/89 cases (17%). Mozart system results informed the necessity to perform a re-excision (n=15). Overall, receiver operating characteristic (ROC) curve analysis showed and area under the ROC curve (AUC) of 0.82 for the Mozart system versus 0.65 for IM. ROC analysis of radiological findings with microcalcifications showed an AUC of 0.92 for the Mozart system versus 0.74 for IM, whereas AUC in cases with no microcalcifications were 0.87 and 0.75, respectively. CONCLUSION: Intra-operative digital breast tomosynthesis with a dedicated device provides more information (better accuracy) than IM and facilitated a reduction in re-excision rates.

Radiation dose with digital breast tomosynthesis compared to digital mammography: per-view analysis.

OBJECTIVES: To compare radiation dose delivered by digital mammography (FFDM) and breast tomosynthesis (DBT) for a single view. METHODS: 4,780 FFDM and 4,798 DBT images from 1,208 women enrolled in a screening trial were used to ground dose comparison. Raw images were processed by an automatic software to determine volumetric breast density (VBD) and were used together with exposure data to compute the mean glandular dose (MGD) according to Dance's model. DBT and FFDM were compared in terms of operation of the automatic exposure control (AEC) and MGD level. RESULTS: Statistically significant differences were found between FFDM and DBT MGDs for all views (CC: MGDFFDM=1.366 mGy, MGDDBT=1.858 mGy; p<0.0001; MLO: MGDFFDM=1.374 mGy, MGDDBT=1.877 mGy; p<0.0001). Considering the 4,768 paired views, Bland-Altman analysis showed that the average increase of DBT dose compared to FFDM is 38 %, and a range between 0 % and 75 %. CONCLUSIONS: Our findings show a modest increase of radiation dose to the breast by tomosynthesis compared to FFDM. Given the emerging role of DBT, its use in conjunction with synthetic 2D images should not be deterred by concerns regarding radiation burden, and should draw on evidence of potential clinical benefit. KEY POINTS: • Most studies compared tomosynthesis in combination with mammography vs. mammography alone. • There is some concern about the dose increase with tomosynthesis. • Clinical data show a small increase in radiation dose with tomosynthesis. • Synthetic 2D images from tomosynthesis at zero dose reduce potential harm. • The small dose increase should not be a barrier to use of tomosynthesis.

Preoperative MRI evaluation of lesion-nipple distance in breast cancer patients: thresholds for predicting occult nipple-areola complex involvement.

AIM: To identify clinically occult nipple-areola complex (NAC) involvement using preoperative magnetic resonance imaging (MRI), to inform selection of patients eligible for nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM). MATERIAL AND METHODS: This was a retrospective study of 195 patients, who had preoperative breast MRI (February 2011 to January 2017) before undergoing surgical treatments (NSM or SSM) for newly diagnosed breast cancer. Tumour features at MRI (mass or non-mass lesion, diameter, lesion-NAC distance [LND]) and pathology (lesion diameter, histopathological type, receptor status) were recorded, as well as the type of surgery (NSM/SSM) and presence (NAC+) or absence (NAC-) of tumour at intraoperative evaluation of retroareolar tissue. Mann-Whitney test, Fisher's exact test, logistic regression, and receiver operating characteristic (ROC) curve analysis were used for analysis of NAC+ versus NAC- to assess variables that predict NAC tumoural involvement. RESULTS: Over the study period, NAC+ was proven histologically in 71/200 (35.5%) surgical treatments, while there were 129/200 NAC- (72 NSM and 128 SSM performed). LND at MRI was statistically (p<0.001) lower in NAC+ patients than in NAC- patients. The area under the ROC curve (0.82, 95% confidence interval [CI]: 0.76-0.88) indicated 10 mm as the best cut-off, with sensitivity of 82%, specificity of 72%, and accuracy of 79%. A 5-mm cut-off enhanced sensitivity, whereas a 15-mm cut-off favoured specificity. CONCLUSIONS: MRI is a useful tool for identifying NAC+ patients; a 10-mm cut-off for LND assists selection of patients for NSM, although intraoperative retroareolar tissue examination remains mandatory.

Digital breast tomosynthesis as an adjunct to digital mammography for detecting and characterising invasive lobular cancers: a multi-reader study.

AIM: To examine the interpretive performance of digital breast tomosynthesis (DBT) as an adjunct to digital mammography (DM) compared to DM alone in a series of invasive lobular carcinomas (ILCs) and to assess whether DBT can be used to characterise ILC. MATERIALS AND METHODS: A retrospective, multi-reader study was conducted of 83 mammographic examinations of women with 107 newly diagnosed ILCs ascertained at histology. Consenting women underwent both DM and DBT acquisitions. Twelve radiologists, with varying mammography experience, interpreted DM images alone, reporting lesion location, mammographic features, and malignancy probability using the Breast Imaging-Reporting and Data System (BI-RADS) categories 1-5; they then reviewed DBT images in addition to DM, and reported the same parameters. Statistical analyses compared sensitivity, false-positive rates (FPR), and interpretive performance using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), for reading with DM versus DM plus DBT. RESULTS: Multi-reader pooled ROC analysis for DM plus DBT yielded AUC=0.89 (95% confidence interval [CI]: 0.88-0.91), which was significantly higher (p<0.0001) than DM alone with AUC=0.84 (95% CI: 0.82-0.86). DBT plus DM significantly increased pooled sensitivity (85%) compared to DM alone (70%; p<0.0001). FPR did not vary significantly with the addition of DBT to DM. Interpreting with DBT (compared to DM alone) increased the correct identification of ILCs depicted as architectural distortions (84% versus 65%, respectively) or as masses (89% versus 70%), increasing interpretive performance for both experienced and less-experienced readers; larger gains in AUC were shown for less-experienced radiologists. Multifocal and/or multicentric and bilateral disease was more frequently identified on DM with DBT. CONCLUSION: Adding DBT to DM significantly improved the accuracy of mammographic interpretation for ILCs and contributed to characterising disease extent.

Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ.

BACKGROUND: MRI has been used increasingly in the diagnosis and management of women with invasive breast cancer. However, its usefulness in the preoperative assessment of ductal carcinoma in situ (DCIS) remains questionable. A meta-analysis was conducted to examine the effects of MRI on surgical treatment of DCIS by analysing studies comparing preoperative MRI with conventional preoperative assessment. METHODS: Using random-effects modelling, the proportion of women with various outcomes in the MRI versus no-MRI groups was estimated, and the odds ratio (OR) and adjusted OR (adjusted for study-level median age) for each model were calculated. RESULTS: Nine eligible studies were identified that included 1077 women with DCIS who had preoperative MRI and 2175 who did not. MRI significantly increased the odds of having initial mastectomy (OR 1·72, P = 0·012; adjusted OR 1·76, P = 0·010). There were no significant differences in the proportion of women with positive margins following breast-conserving surgery (BCS) in the MRI and no-MRI groups (OR 0·80, P = 0·059; adjusted OR 1·10, P = 0·716), nor in the necessity of reoperation for positive margins after BCS (OR 1·06, P = 0·759; adjusted OR 1·04, P = 0·844). Overall mastectomy rates did not differ significantly according to whether or not MRI was performed (OR 1·23, P = 0·340; adjusted OR 0·97, P = 0·881). CONCLUSION: Preoperative MRI in women with DCIS is not associated with improvement in surgical outcomes.

Metastatic breast cancer in young women: a population-based cohort study to describe risk and prognosis.

BACKGROUND: There is limited information on the risk of metastatic breast cancer (MBC) to inform younger women, particularly those under 40 years. AIMS: We conducted a retrospective analysis of a population-based cohort study to describe the risk, site and prognosis of MBC in young women under 40 years with an initial diagnosis of non-metastatic breast cancer and compared with older women. METHODS: Data were extracted from the New South Wales Central Cancer Registry and the Admitted Patient Data Collection database between 2001-2007. Main outcome measures were 5-year cumulative incidence of MBC, prognostic factors for MBC and overall survival (OS) from the date of MBC diagnosis. RESULTS: Three hundred and ninety-five (6%) of 6640 women with non-metastatic BC were <40 years. The 5-year cumulative incidence of MBC was 24% (95% CI 20-29%) for women <40 years with non-metastatic BC, compared with 9% (95% CI 9-10%) for women ≥40 years. Significant independent risk factors for MBC ≤ 5 years were age <40, regional disease at diagnosis, low socioeconomic status and the presence of other non-breast primary. At first record of MBC, visceral sites were more common for women <40 years than ≥40 (54% vs 43%; P = 0.03). Median survival for women with MBC within 5 years was not significantly different between young and older women (<40 years 18 months vs ≥40 years 14 months; log-rank P = 0.21). CONCLUSIONS: Women with non-metastatic BC before age 40 have a higher 5-year risk of developing MBC than older women. There were no significant differences in median survival following MBC between young and older women.

The impact of breast density notification on psychosocial outcomes in racial and ethnic minorities: A systematic review.

BACKGROUND: High breast density is an independent risk factor for breast cancer and decreases the sensitivity of mammography. This systematic review synthesizes the evidence on the impact of breast density (BD) information and/or notification on women's psychosocial outcomes among women from racial and ethnic minority groups. METHODS: A systematic search was performed in March 2023, and the articles were identified using CINHAL, Embase, Medline, and PsychInfo databases. The search strategy combined the terms "breast", "density", "notification" and synonyms. The authors specifically kept the search terms broad and did not include terms related to race and ethnicity. Full-text articles were reviewed for analysis by race, ethnicity and primary language of participants. Two authors evaluated the eligibility of studies with verification from the study team, extracted and crosschecked data, and assessed the risk of bias. RESULTS: Of 1784 articles, 32 articles published from 2003 to 2023 were included. Thirty-one studies were conducted in the United States and one in Australia, with 28 quantitative and four qualitative methodologies. The overall results in terms of breast density awareness, knowledge, communication with healthcare professionals, screening intentions and supplemental screening practice were heterogenous across studies. Barriers to understanding BD notifications and intentions/access to supplemental screening among racial and ethnic minorities included socioeconomic factors, language, health literacy and medical mistrust. CONCLUSIONS: A one-size approach to inform women about their BD may further disadvantage racial and ethnic minority women. BD notification and accompanying information should be tailored and translated to ensure readability and understandability by all women.

Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy.

BACKGROUND: Magnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI's agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of agreement. METHODS: A systematic literature search was undertaken. Mean differences (MDs) in tumour size between MRI or comparator tests and pathology were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated from a pooled variance by assuming equal variance of the differences across studies. RESULTS: Data were extracted from 19 studies (958 patients). The pooled MD between MRI and pathology from six studies was 0.1 cm (95% LOA: -4.2 to 4.4 cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm) was observed, with comparable LOA (two studies). Overestimation was lower for MRI (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: -0.3 cm). The LOA for mammography and clinical examination were wider than that for MRI. Percentage agreement between MRI and pathology was greater than that of comparator tests (six studies). The range of Pearson's/Spearman's correlations was wide (0.21-0.92; 16 studies). Inconsistencies between MDs, percentage agreement and correlations were common. CONCLUSION: Magnetic resonance imaging appears to slightly overestimate pathologic size, but measurement errors may be large enough to be clinically significant. Comparable performance by US was observed, but agreement with pathology was poorer for mammography and clinical examination. Percentage agreement can provide supplementary information to MDs and LOA, but Pearson's/Spearman's correlation does not provide evidence of agreement and should be avoided. Further comparisons of MRI and other tests using the recommended methods are warranted.

Which screening strategy should be offered to women with BRCA1 or BRCA2 mutations? A simulation of comparative cost-effectiveness.

BACKGROUND: There is no consensus on the most effective strategy (mammography or magnetic resonance imaging (MRI)) for screening women with BRCA1 or BRCA2 mutations. The effectiveness and cost-effectiveness of the Dutch, UK and US screening strategies, which involve mammography and MRI at different ages and intervals were evaluated in high-risk women with BRCA1 or BRCA2 mutations. METHODS: Into a validated simulation screening model, outcomes and cost parameters were integrated from published and cancer registry data. Main outcomes were life-years gained and incremental cost-effectiveness ratios. The simulation was situated in the Netherlands as well as in the United Kingdom, comparing the Dutch, UK and US strategies with the population screening as a reference. A discount rate of 3% was applied to both costs and health benefits. RESULTS: In terms of life-years gained, the strategies from least to most cost-effective were the UK, Dutch and US screening strategy, respectively. However, the differences were small. Applying the US strategy in the Netherlands, the costs were €43 800 and 68 800 for an additional life-year gained for BRCA1 and BRCA2, respectively. At a threshold of €20 000 per life-year gained, implementing the US strategy in the Netherlands has a very low probability of being cost-effective. Stepping back to the less-effective UK strategy would save relatively little in costs and results in life-years lost. When implementing the screening strategies in the United Kingdom, the Dutch, as well as the US screening strategy have a high probability of being cost-effective. CONCLUSION: From a cost-effectiveness perspective, the Dutch screening strategy is preferred for screening high-risk women in the Netherlands as well as in the United Kingdom.

Imaging bone metastases in breast cancer: evidence on comparative test accuracy.

BACKGROUND: Numerous imaging modalities may be used to detect bone metastases (BM) in women with breast cancer. METHODS: Systematic evidence review, including quality appraisal, of studies reporting on comparative imaging accuracy for detection of BM from breast cancer. RESULTS: Eligible studies (N = 16) included breast cancer subjects who had imaging evaluation for suspected BM or for staging/restaging in suspected local or distant relapse. Median prevalence of BM was 34.0% (range 10.0%-66.7%). There was substantial heterogeneity in the quality of reference standards and in the prevalence of BM, which could account for some of the differences in reported comparative accuracy. Most frequently, bone scan (BS) was compared with newer imaging modalities in subjects selected to both tests; therefore, results could be affected by selection bias. There was some evidence that positron emission tomography (PET), and limited evidence that PET/computed tomography (CT), CT, and magnetic resonance imaging (MRI), may provide small increments in accuracy relative to BS as add-on tests; there was little evidence regarding single photon emission computed tomography or whole-body MRI. CONCLUSIONS: There is some evidence of enhanced incremental accuracy for some of the above-mentioned tests where used as add-on in subjects selected to more than one imaging modality, with little evidence to support their application as a replacement to BS in first-line imaging of BM. PET/CT appears to have high accuracy and is recommended for further evaluation.

Proportional incidence and radiological review of large (T2+) breast cancers as surrogate indicators of screening programme performance.

OBJECTIVES: Surrogate measures of screening performance [e.g. interval cancer (IC) proportional incidence] allow timely monitoring of sensitivity and quality. This study explored measures using large (T2+) breast cancers as potential indicators of screening performance. METHODS: The proportional incidence of T2+ cancers (observed/expected cases) in a population-based screening programme (Trento, 2001-2009) was estimated. A parallel review of 'negative' preceding mammograms for screen-detected T2+ and for all ICs, using 'blinded' independent readings and case-mixes (54 T2+, 50 ICs, 170 controls) was also performed. RESULTS: T2+ cancers were observed in 168 screening participants: 48 at first screen, 67 at repeat screening and 53 ICs. The T2+ estimated proportional incidence was 68% (observed/expected = 168/247), corresponding to an estimated 32% reduction in the rate of T2+ cancers in screening participants relative to that expected without screening. Majority review classified 27.8% (15/54) of T2+ and 28% (14/50) of ICs as screening error (P = 0.84), with variable recall rates amongst radiologists (8.8-15.2%). CONCLUSIONS: T2+ review could be integrated as part of quality monitoring and potentially prove more feasible than IC review for some screening services. KEY POINTS: • Interval breast cancers, assumed as screening failures, are monitored to estimate screening performance • Large (T2+) cancers at screening may also represent failed prior screening detection • Analysis of T2+ lesions may be more feasible than assessing interval cancers • Analysis of T2+ cancers is a potential further measure of screening performance.

De novo and recurrent metastatic breast cancer - A systematic review of population-level changes in survival since 1995.

BACKGROUND: Advances in breast cancer (BC) care have reduced mortality, but their impact on survival once diagnosed with metastasis is less well described. This systematic review aimed to describe population-level survival since 1995 for de novo metastatic BC (dnMBC) and recurrent MBC (rMBC). METHODS: We searched MEDLINE 01/01/1995-12/04/2021 to identify population-based cohort studies of MBC reporting overall (OS) or BC-specific survival (BCSS) over time. We appraised risk-of-bias and summarised survival descriptively for MBC diagnoses in 5-year periods from 1995 until 2014; and for age, hormone receptor and HER2 subgroups. FINDINGS: We identified 20 eligible studies (14 dnMBC, 1 rMBC, 5 combined). Potential sources of bias in these studies were confounding and shorter follow-up for the latest diagnosis period.For dnMBC, 13 of 14 studies reported improved OS or BCSS since 1995. In 2005-2009, the median OS was 26 months (range 24-30), a median gain of 6 months since 1995-1999 (range 0-9, 4 studies). Median 5-year OS was 23% in 2005-2009, a median gain of 7% since 1995-1999 (range -2 to 14%, 4 studies). For women ≥70 years, the median and 5-year OS was unchanged (1 study) with no to modest difference in relative survival (range: -1·9% (p = 0.71) to +2·1% (p = 0.045), 3 studies). For rMBC, one study reported no change in survival between 1998 and 2006 and 2007-2013 (median OS 23 months). For combined MBC, 76-89% had rMBC. Three of four studies observed no change in median OS after 2000. Of these, one study reported median OS improved for women ≤60 years (1995-1999 19·1; 2000-2004 22·3 months) but not >60 years (12·7, 11·6 months). INTERPRETATION: Population-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification. FUNDING: SL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21-001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).

Early detection of second breast cancers improves prognosis in breast cancer survivors.

BACKGROUND: The impact of early detection of second breast cancers in women who have survived a primary breast cancer is unknown. We examined the prognostic effect of detection of ipsilateral breast relapse (IBR) or contralateral breast cancer (CBC) in the asymptomatic relative to symptomatic phase. PATIENTS AND METHODS: Subjects were women with histology-verified second (invasive or in situ) breast cancer (N = 1044) in a breast centre in Florence (1980-2005). Symptom status, test, tumour stage, and outcomes data were obtained from clinical records and linkage with mortality registry. Disease-specific survival was measured from first cancer diagnosis to avoid lead-time bias. Sensitivity analysis was used to allow for length-time bias. RESULTS: Second cancers (IBR = 455; CBC = 589; median age 60 years) were diagnosed in 699 asymptomatic and 345 symptomatic women (67% versus 3%, P < 0.0001). Mammography was more sensitive than clinical examination (86% versus 57%, P < 0.0001); however, 13.8% of cases were only identified clinically. Asymptomatic cancers were smaller than symptomatic for both IBR (P < 0.001) and CBC (P < 0.001). Early-stage tumours were more frequent in asymptomatic (58.1%) than symptomatic (22.6%) women (P < 0.0001). Fewer women with asymptomatic than symptomatic CBC had node metastases (P = 0.0001). Hazard ratio (HR) for asymptomatic (relative to symptomatic) detection was 0.51 (0.32-0.80) for IBR, 0.53 (0.36-0.78) for CBC, and 0.53 (0.40-0.72) in all subjects (P < 0.0001). Length bias-adjusted HRs ranged from 0.53 to 0.73. CONCLUSION: Detection of second breast cancers in the asymptomatic phase leads to detection of early-stage cancer and improves relative survival by between 27% and 47%.

Towards evidence-based follow-up intervals for breast cancer survivors: Estimates of the preclinical detectable phase of contralateral second breast cancer.

PURPOSE: Follow-up schemes in breast cancer survivors are predominantly consensus-based. To determine evidence-based follow-up intervals, estimates of sensitivity of the screening test(s) and duration of the preclinical detectable phase (PCDP) are key. We estimated the sensitivity and the duration of the PCDP of clinical breast examination (CBE) and mammography for the detection of contralateral second breast cancers (CBC) in breast cancer survivors. METHODS: Women with a CBC (N = 589) diagnosed in Florence between 1980 and 2005 were included. Test sensitivity and the duration of PCDP were estimated using a simple exponential model of PCDP duration. Analyses were stratified by follow-up period (0-5 vs. >5 years after primary diagnosis) and age at CBC diagnosis (<50 vs. ≥50 years). RESULTS: For CBE, test sensitivity was 55% and the duration of the PCDP 16 months. Mammography sensitivity was 91% and duration of the PCDP 35 months. Stratified analyses showed a higher test sensitivity for CBE for women aged <50 (70% vs. 51%). No difference in the duration of PCDP of CBE was found. For mammography, test sensitivity and the duration of the PCDP were higher for women with longer follow-up and in older women. CONCLUSIONS: Poor test sensitivity for CBE with a shorter duration of the PCDP compared with mammography were observed. Mammography had high test sensitivity and the potential to detect CBCs early. The estimated duration of the PCDP (35 months) was considerably longer than the recommended follow-up interval (12 months). Future studies are needed to determine whether a longer follow-up interval is appropriate.

Second breast cancers in a Tuscan case series: characteristics, prognosis, and predictors of survival.

Little is known about long-term outcomes following a second breast cancer diagnosis. We describe the epidemiology, characteristics and prognosis of second breast cancers in an Italian cohort. We identified women with two breast cancer diagnoses from 24 278 histology records at a Tuscan breast cancer service between 1980 and 2005, and determined their survival status. Disease-specific survival from second diagnosis was examined using Cox regression analyses. Second cancers were identified in 1044 women with a median age of 60 years. In all 455 were ipsilateral relapses and 589 were contralateral cancers. Median time between first and second diagnosis was 63.4 months. The majority of second cancers was small invasive or in situ tumours. Estimated 10-year survival from a second cancer diagnosis was 78%. Survival was poorest when the second cancer was large (HR=2.26) or node-positive (HR=3.43), when the time between the two diagnoses was <5 years (HR=1.45), or when the diagnosis was in an earlier epoch (HR=2.20). Second tumours were more likely to be large or node-positive if the first breast cancer had these features. Prognosis following a second breast cancer in this cohort was generally good. However, large or node-positive second tumours, and shorter intervals between diagnoses were indicators of poorer survival.

Poor hormone receptor expression in East African breast cancer: evidence of a biologically different disease?

BACKGROUND: Few studies have examined breast cancer hormone receptor expression in Africans. We report on the hormone receptor profile of breast cancer in East Africans in the largest prospective study for this region. METHODS: Consecutive breast cancer presentations to a hospital in Kijabe (2001-2007) were included. Demographic, clinical, and test data were collected. ER/PR and Her2 testing was based on immunohistochemistry (IHC). RESULTS: There were 129 subjects (median 47 years), most had invasive ductal cancer and locally advanced disease and/or metastases. ER/PR testing was done in 120: 24% had ER-positive tumours, 34% were ER- and/or PR-positive, 10% were ER-negative but PR-positive tumours, and 66% were negative for ER and PR. ER/PR positivity was not associated with stage (P = 0.28) and was not related to age, parity, menopausal status, or node metastases. Increasing tumour grade was associated with PR expression (P = 0.02) with decreasing frequency of PR positive tumours as histological grade increased; there was weak evidence of an association between grade and ER expression (P = 0.06). Of cases tested, 26.5% overexpressed Her2. CONCLUSIONS: Breast cancer in Kijabe is an advanced-stage disease, comprised mainly of poorly differentiated cancers that are less likely to be hormone sensitive (across all stages of disease). ER/PR testing of all those affected by breast cancer should be supported as a global priority in cancer control. International and inter-African research collaborations are needed to allow genetic detailing of tumours in indigenous Africans to assess possible racial heterogeneity in the biology of breast cancer.

A systematic review of the effectiveness of magnetic resonance imaging (MRI) as an addition to mammography and ultrasound in screening young women at high risk of breast cancer.

Breast magnetic resonance imaging (MRI) has been proposed as an additional screening test for young women at high risk of breast cancer in whom mammography alone has poor sensitivity. We conducted a systematic review to assess the effectiveness of adding MRI to mammography with or without breast ultrasound and clinical breast examination (CBE) in screening this population. We found consistent evidence in 5 studies that adding MRI provides a highly sensitive screening strategy (sensitivity range: 93-100%) compared to mammography alone (25-59%) or mammography plus ultrasound+/-CBE (49-67%). Meta-analysis of the three studies that compared MRI plus mammography versus mammography alone showed the sensitivity of MRI plus mammography as 94% (95%CI 86-98%) and the incremental sensitivity of MRI as 58% (95%CI 47-70%). Incremental sensitivity of MRI was lower when added to mammography plus ultrasound (44%, 95%CI 27-61%) or to the combination of mammography, ultrasound plus CBE (31-33%). Estimates of screening specificity with MRI were less consistent but suggested a 3-5-fold higher risk of patient recall for investigation of false positive results. No studies assessed as to whether adding MRI reduces patient mortality, interval or advanced breast cancer rates, and we did not find strong evidence that MRI leads to the detection of earlier stage disease. Conclusions about the effectiveness of MRI therefore depend on assumptions about the benefits of early detection from trials of mammographic screening in older average risk populations. The extent to which high risk younger women receive the same benefits from early detection and treatment of MRI-detected cancers has not yet been established.

Image-detected 'probably benign' breast lesions: a significant reason for referral from primary care.

In Australia, and many health care provider systems, primary care physicians are the first to see women with breast symptoms and are responsible for making decisions on whether to investigate and when to refer to specialist teams. We present an audit of new patient referrals from primary care triaged to a 'low-risk' (low likelihood of cancer) clinic on the basis of benign findings. The most common reason for referral was 'breast lump' (38%) followed by 'image-detected' abnormality (26%.) We have identified that (outside of population screening services) many women are being referred from primary care to specialist clinics for management of screen-detected lesions considered benign on imaging. Further research is needed to identify the reasons for such referrals and to develop appropriate educational strategies and clinical policy, both for the primary care and the specialist breast practitioner.