Final Results of the Prospective FH02 Mammographic Surveillance Study of Women Aged 35-39 at Increased Familial Risk of Breast Cancer.

BACKGROUND: Many women who are at increased risk of breast cancer due to a mother or sister diagnosed with breast cancer aged under 40 do not currently qualify for surveillance before 40 years of age. There are almost no available data to assess whether mammography screening aged 35-39 years would be effective in this group, in terms of detection of breast cancer at an early stage or cost effective. METHODS: A cohort screening study (FH02) with annual mammography was devised for women aged 35-39 to assess the sensitivity and screening performance and potential survival of women with identified tumours. FINDINGS: 2899 women were recruited from 12/2006-12/2015. These women underwent 12,086 annual screening mammograms and were followed for 13,365.8 years. A total of 55 breast cancers in 54 women occurred during the study period (one bilateral) with 50 cancers (49 women) (15 CIS) adherent to the screening. Eighty percent (28/35) of invasive cancers were ≤ 2 cm and 80% also lymph node negative. Invasive cancers diagnosed in FH02 were significantly smaller than the comparable (POSH-unscreened prospective) study group (45% (131/293) ≤ 2 cm in POSH vs 80% (28/35) in FH02 p < 0.0001), and were less likely to be lymph-node positive (54% (158/290, 3 unknown) in POSH vs 20% (7/35) in FH02: p = 0.0002. Projected and actual survival were also better than POSH. Overall radiation dose was not higher than in an older screened population at mean dose on study per standard sized breast of 1.5 mGy. INTERPRETATION: Mammography screening aged 35-39 years detects breast cancer at an early stage and is likely to be as effective in reducing mortality as in women at increased breast cancer risk aged 40-49 years.

Film reading in the East Midlands Breast Screening Programme -- are we missing opportunities for earlier diagnosis?

AIM: To assess whether there are any significant differences in the film-reading histories of interval or screen-detected cancers, and whether this affects stage at diagnosis. MATERIALS AND METHODS: The rates of screen-detected and interval cancers (overall and by radiological categorization) were observed from 268,067 women screened in the East Midlands Breast Screening Programme over 2004-2007 to assess whether there were differences in incidence based on previous film-reading history. Cancers detected at the subsequent screen and film-reading history were analysed to assess whether this affected stage at diagnosis. Analysis undertaken involved cancer detection rates, confidence intervals, and chi-square tests with Monte Carlo simulation. RESULTS: Rates of interval cancers were similar in all groups where at least one reader had indicated recall to assessment (6.1-7.7/1000) and were significantly higher in comparison to women whose previous film-reading outcome was unanimous routine rescreen (2.9/1000; p < 0.001). Four point one percent of interval cancers with no previous recall outcomes were false negatives, which was significantly lower compared to the groups where at least one reader had indicated recall (10.9%; p = 0.005). Cancers detected at the subsequent screen demonstrated no significant difference in prognosis dependent on previous film-reading history (p = 0.503). CONCLUSION: The prognosis of screen-detected cancers was similar and few cancers were false negatives regardless of film-reading history at the previous screen.

Mammographic surveillance in women aged 35-39 at enhanced familial risk of breast cancer (FH02).

Although there have been encouraging recent studies showing a potential benefit from annual mammography in women aged 40-49 years of age with an elevated breast cancer risk due to family history there is little evidence of efficacy in women aged <40 years of age. A prospective study (FH02) has been developed to assess the efficacy of mammography screening in women aged 35-39 years of age with a lifetime breast cancer risk of ≥ 17 % who are not receiving MRI screening. Retrospective analyses from five centres with robust recall systems identified 47 breast cancers (n = 12 in situ) with an interval cancer rate of 15/47 (32%). Invasive tumour size, lymph node status and current vital status were all significantly better than in two control groups of unscreened women (including those with a family history) recruited to the POSH study. Further evaluation of the prospective arm of FH02 is required to assess the potential added value of digital mammography and the cancer incidence rates in moderate and high risk women in order to inform cost effectiveness analyses.

Skin sparing mastectomy and immediate breast reconstruction: a review.

AIMS: Skin Sparing Mastectomy (SSM) is widely practised now in major centres which manage large numbers of breast cancer but anxiety still exists over the safety of SSM both from oncological and aesthetic points of view. We aim to review literature to date in SSM and summarise and discuss the current evidence. METHODS: Studies were identified by an online search of the English language literature in the PubMed database till April 2012 followed by an extensive review of bibliographies from relevant articles. RESULTS: There is abundance of evidence with regards to the safety of SSM both oncologically and aesthetically especially in immediate breast reconstruction. The use of SSM technique broadens the repertoire of oncoplastic techniques and at the same time facilitates such techniques by preserving patient's native skin and anatomical landmarks. CONCLUSIONS: SSM is a safe technique providing better cosmetic outcome without compromising oncological safety as per the current evidence. However, prospective data collection of its application in various newer types of reconstructions, and continuing long-term follow-up of current data series would be prudent to evaluate long-term outcomes.

Why do hospital mastectomy rates vary? Differences in the decision-making experiences of women with breast cancer.

BACKGROUND: Hospital mastectomy rates vary. This study explores the relationship between mastectomy rates and breast cancer patients' consultation and decision-making experiences with specialist clinicians. METHODS: Qualitative semi-structured interviews were conducted with 65 patients from three purposively selected breast units from a single UK region. Patients provided with a choice of breast cancer surgery (breast conservation therapy (BCT) or mastectomy) were purposively recruited from high, medium and low case-mix-adjusted mastectomy rate units. RESULTS: Low mastectomy rate unit patients' consultation and decision-making experiences were markedly different to those of the medium and high mastectomy rate breast units. Treatment variation was associated with patients' perception of the most reassuring and least disruptive treatment; the content and style of information provision (equipoise or directed); level of patient participation in decision making; the time and process of decision making and patient autonomy in decision making. The provision of more comprehensive less directive information and greater autonomy, time and support of independent decision making were associated with a lower uptake of BCT. CONCLUSION: Variation in hospital mastectomy rates was associated with differences in the consultation and decision-making experiences of breast cancer patients. Higher mastectomy rates were associated with the facilitation of more informed autonomous patient decision making.

Effect of evening primrose oil on clinically diagnosed fibroadenomas.

The effects of oil of evening primrose oil on fibroadenomas was assessed over a 6-month period. Eleven out of 21 (52%) of fibroadenomas receiving evening primrose oil and 8 out of 19 (42%) controls reduced in size. This study demonstrates that evening primrose oil does not significantly effect the natural history of breast fibroadenomas.

Screening women aged less than 50 years with a family history of breast cancer.

Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.

The ultrasound appearances of galactocoeles.

Galactocoeles are an uncommon cause of breast masses, usually occurring in lactating women. The purpose of this study was to review the ultrasound (US) features of galactocoeles presenting to the Nottingham Breast Unit. Eight women with galactocoeles were scanned during 1994 and 1995. All the scans were abnormal, 50% of lesions were cystic or multicystic, 37% mixed cystic/solid and 13% appeared solid. A fat-fluid level was seen in only one case. Two of the cystic/solid lesions had ill defined solid components, raising the possibility of an intracystic carcinoma. All cases were confirmed by the aspiration of milk and clinical resolution following aspiration.

Screening interval breast cancers: mammographic features and prognosis factors.

PURPOSE: To review the mammographic features of screening interval breast cancers and to compare the tumor size, histologic grade, and lymph node involvement with those in screening-detected and unscreened symptomatic cancers. MATERIALS AND METHODS: Screening mammography was performed in 72,773 women aged 50-64 years. Ninety interval cancers were identified in 89 women. The mammographic and histopathologic features of these cancers were analyzed. RESULTS: At review of the screening mammograms, interval cancers were classified into four groups: 51 true-positive, 20 false-negative, seven mammographically occult, and 12 unclassified. The most common missed abnormality in the false-negative cases was architectural distortion. Interval cancers were larger, of higher grade, and more likely to have lymph node involvement than screening-detected tumors and were of similar size, histologic grade, and stage of lymph node involvement as symptomatic tumors. CONCLUSION: Prognosis in interval cancers is similar to that in symptomatic, unscreened tumors and statistically significantly worse than that in screening-detected cancers.

Safe selection criteria for breast conservation without radical excision in primary operable invasive breast cancer.

In a previous series from this unit of 263 women with primary operable breast cancer treated by macroscopic lumpectomy and breast irradiation, local recurrence was high. An audit at a median follow up of 36 months showed 56 (21%) ipsilateral breast recurrences. Eighteen of these recurrences were aggressive and uncontrolled. Multivariate analysis shows patient age, lymphovascular invasion, tumour size and nodal status to be predictive of local recurrence (Locker AP, et al., Br J Surgery 1989, 76, 890-894). New selection criteria for breast conservation were defined based on these data and also on securing an adequate clear margin of excision. In a subsequent prospective series of 275 women fulfilling these criteria, 6 women (2.2%) developed ipsilateral breast recurrence at the same median follow up of 36 months. In none was this uncontrolled and aggressive. Breast conservation, without radical excision, is safe as long as the selection criteria described are followed.

Case report: fibromatosis of the breast in a male patient.

Fibromatosis of the breast is an uncommon disease, although several series of this condition in females have been reported in the literature. We present the first case to be described in a male patient.

Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma.

In a study of 1529 patients with primary operable breast carcinoma we have assessed the effect of applying both histological grade and tumour type to determine their comparative value as prognostic factors in human breast cancer. The prognostic group the patient was placed in, based on histological type alone, was less accurate than using grade and type together for many tumours. The importance of performing histological grading of ductal/no special type carcinoma (50% of the women in this series) is confirmed in this series. The 10-year-survival varied from 76% for women with grade 1 carcinoma to 39% for those with grade 3 tumours. Some of the 'special types' of breast carcinoma including tubular, tubulo-lobular, invasive cribriform and grade 1 mucinous carcinomas behaved as would be predicted, with a greater than 80% 10-year-survival in this series. Others, including grade 2 mucinous carcinomas, however, behaved less well with a 60% to 80% 10-year-survival. Indeed, many of the histological tumour types including tubular mixed, ductal/no special type, mixed ductal with special type and lobular carcinomas of classical, solid or mixed types showed a variation in behaviour that could not be predicted by typing alone. Histological grade and tumour type, when used together, more accurately predicted prognosis. In multivariate analysis of a larger group of 2658 cases of primary breast carcinomas (including the 1529 study cases) when histological grade, lymph node status and tumour size were entered, grade was the most important factor in predicting for survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival.

The 'growth fraction' of tumours can now be assessed on paraffin sections of tissues using the monoclonal antibody MIB1 by a microwave antigen retrieval technique. The MIB1 labelling index was studied using a CAS 200 image analyser in 177 tumours from women with primary operable breast carcinoma in whom long-term follow-up data were known. Statistical analysis showed a strong association between the MIB1 labelling index and histological grade (P < 0.001), tumour size (P = 0.002), tumour type (P < 0.001) and also patient survival (P < 0.001). No association with lymph node stage (P = 0.974) or regional recurrence (P = 0.185), the presence or absence of distant metastases (P = 0.418), patient age (P = 0.309), menopausal status (P = 0.181) or oestrogen receptor status (P = 0.401) was found in this group of patients. In multivariate analysis for survival, when histological grade, lymph node stage and tumour size were included as well as the MIB1 labelling index, each was found to be of independent significance. If histological grade was not included, MIB1 replaced it as the most important variable predicting for survival in this group of patients. The results suggest that the tumour growth fraction, as assessed by the MIB1 labelling index, is an important predictor of survival.

Pathological-radiological correlations in benign lesions excised during a breast screening programme.

Benign biopsies are an inevitable part of any screening programme. They add significantly to the psychological and financial 'cost' of screening and so should be kept to a minimum. To identify possible means of reducing these false positive results we have reviewed the mammographic features of 108 benign lesions removed during prevalent round screening and correlations were sought with the pathological findings. The commonest mammographic abnormalities leading to benign biopsy were non-comedo type suspicious calcification (29%), poorly defined mass (21%), architectural distortion (19%) and a well defined mass (18%). The histological correlates were: non-comedo type suspicious calcification (fibrocystic change 60%, sclerosing adenosis 35%, and radial scar/CSL 13%), poorly defined masses (fibrocystic change 37%, fibroadenomas 37%, and sclerosing adenosis 25%) and architectural distortion (radial scar/CSL 61% and fibrocystic change 26%). Methods of reducing screening provoked benign biopsies are discussed.

The radiological appearances of invasive cribriform carcinoma of the breast. Nottingham Breast Team.

Invasive cribriform carcinoma (ICC) of the breast is characterized by a cribriform histological architecture. It is rare, accounting for 0.6% of breast cancers in Nottingham and has an excellent prognosis. Its radiological features have not been previously described. Preoperative mammograms were available in eight cases (6 symptomatic, 2 screen-detected) and preoperative ultrasound examinations in four. The tumour was mammographically occult in four (50%) cases. The four tumours which were visible on mammography all showed as a large (20-35 mm) spiculated mass and two contained a few flecks of punctate calcification. The ultrasound appearances were not entirely typical of breast carcinoma. Three of four showed an ill-defined, inhomogeneous solid mass, but without the distal acoustic attenuation found in 60-97% of other forms of breast carcinoma. We conclude that ICC has imaging characteristics distinct from tubular carcinoma, which is its closest histological analogue.

Correlations between the mammographic features of ductal carcinoma in situ (DCIS) and C-erbB-2 oncogene expression. Nottingham Breast Team.

PURPOSE: C-erbB-2 oncogene expression is found in 60% of DCIS cases. C-erbB-2 expression in DCIS has been shown to correlate with comedo subtype, large cell size, lymphoid infiltrate, nuclear pleomorphism, multinucleation and high mitotic rate. These findings have led to the suggestion that the subgroup of DCIS that expresses c-erbB-2 may be a biologically definable category with prognostic significance. The purpose of this study was to identify any differences in the mammographic appearances between DCIS which expresses c-erbB-2 and DCIS that does not express this oncogene. MATERIALS AND METHODS: C-erbB-2 staining characteristics and preoperative mammograms were available for review in 126 patients with pure DCIS. All the mammograms were reviewed by a radiologist knowing the patient had DCIS but without any further pathological or immunohistochemical information. RESULTS: C-erbB-2 positive DCIS showed the following features more commonly than c-erbB-2 negative disease: calcification (65 of 71 (92%) vs 28 of 39 (72%), P < 0.01), ductal distribution of calcification (51 of 65 (78%) vs 16 of 28 (57%), P < 0.05), rod-shaped calcification (53 of 65 (82%) vs 15 of 28 (54%), P < 0.01) and granular calcification (63 of 65 (97%) vs 24 of 28 (86%), P < 0.05). C-erbB-2 negative DCIS more commonly showed an abnormal mammogram without calcification than c-erbB-2 positive disease (11 of 39 (28%) vs 6 of 71 (8%), P < 0.01). CONCLUSION: We have demonstrated significant differences in the mammographic features of c-erbB-2 positive and negative disease. As c-erbB-2 expression has been shown to correlate with aggressive histological features, the differences in the mammographic appearances between c-erbB-2 positive and c-erbB-2 negative DCIS may be of practical value.

Blood transfusion and survival in colorectal cancer.

PURPOSE: This study examined the effect of blood transfusion on the prognosis of patients undergoing surgery for colorectal cancer. METHODS: Potentially curative resections for colorectal cancer were performed in 266 patients who were followed prospectively, with a minimum follow-up of 41 months. They were divided into transfused (n = 121) and nontransfused (n = 145) groups according to their perioperative blood transfusion requirements. RESULTS: There were significantly more rectal tumors (chi 2 = 9.5, df = 1, P = 0.002) and fixed tumors (chi 2 = 4.5, df = 1, P = 0.03) in the transfused group. There was no statistically significant difference between the two groups with regard to recurrence-free survival (chi 2 = 1.1, df = 1, P = 0.3) and overall survival (chi 2 = 2.8, df = 1, P = 0.09). CONCLUSION: In this study we have found no statistically significant effect of perioperative blood transfusion on the prognosis of colorectal cancer patients.