Residual lymph node tumour burden following removal of a single axillary sentinel lymph with macrometastatic disease in women with screen-detected invasive breast cancer.

BACKGROUND: Women with screen-detected invasive breast cancer who have macrometastatic disease on axillary sentinel lymph node biopsy (SLNB) are usually offered either surgical axillary node clearance (ANC) or axillary radiotherapy. These treatments can lead to significant complications for patients. The aim of this study was to identify a group of patients who may not require completion ANC. METHODS: Data from the NHS Breast Screening Programme between 1 April 2012 and 31 March 2017 were interrogated to identify women with invasive breast carcinoma and a single sentinel lymph node (SLN) with macrometastatic disease who subsequently proceeded to completion ANC. Univariable and multivariable analyses were performed to identify patients with a single positive SLN who had no further lymph node metastasis on ANC. RESULTS: Of the 2401 women included in the cohort, the presence of non-sentinel node disease was significantly affected by: the number of nodes obtained at SLNB (odds ratio (OR) 0.49 for retrieval of more than 1 node), invasive size of tumour (OR 1.63 for size greater than 20 mm), surgical treatment (OR 1.34 for mastectomy), human epidermal growth factor receptor (HER) 2 status (OR 0.71 for HER2 positivity), and patient age (OR 1.10 for age less than 50 years; OR 1.46 for age greater than 70 years). Patients aged less than 70 years, with tumour size smaller than 2 cm, more than one node retrieved on SLNB, and who had breast-conserving surgery had a lower chance of positive non-sentinel nodes on completion ANC compared with other patients. CONCLUSION: This study, of a purely screen-detected breast cancer cohort, identified a subset of patients who may be spared completion ANC in the event of a single axillary SLN with macrometastasis.

Evaluation of mammographic surveillance services in women aged 40-49 years with a moderate family history of breast cancer: a single-arm cohort study.

BACKGROUND: Women with a significant family history of breast cancer are often offered more intensive and earlier surveillance than is offered to the general population in the National Breast Screening Programme. Up to now, this strategy has not been fully evaluated. OBJECTIVE: To evaluate the benefit of mammographic surveillance for women aged 40-49 years at moderate risk of breast cancer due to family history. The study is referred to as FH01. DESIGN: This was a single-arm cohort study with recruitment taking place between January 2003 and February 2007. Recruits were women aged < 50 years with a family history of breast or ovarian cancer conferring at least a 3% risk of breast cancer between ages 40 and 49 years. The women were offered annual mammography for at least 5 years and observed for the occurrence of breast cancer during the surveillance period. The age group 40-44 years was targeted so that they would still be aged < 50 years after 5 years of surveillance. SETTING: Seventy-four surveillance centres in England, Wales, Scotland and Northern Ireland. PARTICIPANTS: A total of 6710 women, 94% of whom were aged < 45 years at recruitment, with a family history of breast cancer estimated to imply at least a 3% risk of the disease between the ages of 40 and 50 years. INTERVENTIONS: Annual mammography for at least 5 years. MAIN OUTCOME MEASURES: The primary study end point was the predicted risk of death from breast cancer as estimated from the size, lymph node status and grade of the tumours diagnosed. This was compared with the control group from the UK Breast Screening Age Trial (Age Trial), adjusting for the different underlying incidence in the two populations. RESULTS: As of December 2010, there were 165 breast cancers diagnosed in 37,025 person-years of observation and 30,556 mammographic screening episodes. Of these, 122 (74%) were diagnosed at screening. The cancers included 44 (27%) cases of ductal carcinoma in situ. There were 19 predicted deaths in 37,025 person-years in FH01, with an estimated incidence of 6.3 per 1000 per year. The corresponding figures for the Age Trial control group were 204 predicted deaths in 622,127 person-years and an incidence of 2.4 per 1000 per year. This gave an estimated 40% reduction in breast cancer mortality (relative risk = 0.60; 95% confidence interval 0.37 to 0.98; p = 0.04). CONCLUSIONS: Annual mammography in women aged 40-49 years with a significant family history of breast or ovarian cancer is both clinically effective in reducing breast cancer mortality and cost-effective. There is a need to further standardise familial risk assessment, to research the impact of digital mammography and to clarify the role of breast density in this population. TRIAL REGISTRATION: National Research Register N0484114809. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 11. See the HTA programme website for further project information.

Role of routine preoperative lymphoscintigraphy in sentinel node biopsy for breast cancer.

Sentinel node biopsy (SNB) is rapidly emerging as the preferred technique for nodal staging in breast cancer. When radioactive colloid is used, a preoperative lymphoscintiscan is obtained to ease sentinel lymph node (SN) identification. This study evaluates whether preoperative lymphoscintigraphy adds diagnostic accuracy to offset the additional time and cost required. 823 breast cancer patients underwent SNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99 mTc-nanocolloid and Patent Blue V injected peritumourally. The SNB was followed by standard axillary treatment at the same operation. Preoperative lymphoscintigraphy was performed around 3 h after the radioisotope injection. Preoperative lymphoscintigraphy revealed SNs in 593 (72%) of the 823 patients imaged. SN visualisation on lymphoscintigraphy was less successful in large tumours and tumours involving the upper outer quadrant of the breast (P=0.046, P<0.001, respectively). Lymphoscintigraphy showed internal mammary sentinel nodes in 9% (62/707) patients. The SN was identified intraoperatively in 98% (581) patients who had SN visualised on preoperative lymphoscintigraphy, with a false-negative rate of 7%. In patients who did not have SN visualised on preoperative lymphoscintigraphy, the SN was identified at operation in 90% (204) patients, with a false-negative rate of 7%. The SN identification rate was significantly higher in patients with SN visualised on preoperative lymphoscintigraphy (P<0.001). SN identification rate intraoperatively using the gamma probe was significantly higher in the SN visualised group compared with the SN non-visualised group (95% vs. 68%; chi square (1 degrees of freedom (df)) P<0.001. There was no statistically significant difference in the false-negative rate and the operative time between the two groups. A mean of 2.3 (standard deviation (SD) 1.3) SNs per patient were removed in patients with SN visualised on preoperative lymphoscintigraphy compared with 1.8 (SD 1.2) in patients with no SN visualised on lymphoscintigraphy (P<0.001). Although SN visualisation on preoperative lymphoscintigraphy significantly improved the intraoperative SN localisation rate, SN was successfully identified in 90% of patients with no SN visualisation on lymphoscintigraphy. Given the time and cost required to perform routine preoperative lymphoscintigraphy, these data suggest that it may not be necessary in all cases. It may be valuable for surgeons in the learning phase to shorten the learning curve and in patients who have increased risk of intraoperative failed localisation (obese or old patients). A negative preoperative lymphoscintiscan predicts the inability to localise with the hand-held gamma probe. Therefore, if the SN is not visualised on lymphoscintigraphy then the addition of intraoperative blue dye is recommended to increase the likelihood of SN identification.

Sentinel lymph node biopsy in male breast cancer patients.

The concept of sentinel node biopsy has been validated for female breast cancer patients whereas, ALND remains the standard of care for male breast cancer patients with similar tumours. We evaluated the results of SLN biopsy in male breast cancer patients with clinically negative axillae. This study included all male breast cancer patients who underwent SLN biopsy between February 1998 and October 2003. All patients had negative axillae on clinical examination. All patients underwent pre-operative lymphoscintigraphy. SLN biopsy was performed using a combination of Patent blue V and 99mTc-radiolabelled colloidal albumin injected peritumourally. Nine patients, 26-79 years of age, were included in the study. Pre-operative lymphoscinitgraphy identified SLNs in all patients. Intraoperatively, SLNs were successfully localised in all patients. The mean number of SLNs encountered was 2.4. Five patients had a positive SLN, four a negative SLN. Five patients (one with a negative SLN, four with a positive SLN) had been elected pre-operatively to undergo ALND regardless of findings on SLN biopsy. ALND confirmed the SLN to be negative in one patient (false-negative rate: 0%) and three of the four patients with positive SLN(s) had additional positive nodes in the axilla. SLN biopsy accurately predicted axillary lymph node status in these five patients. These findings compare favourably with findings reported in the literature regarding SLN biopsy in female breast cancer patients. SLN biopsy accurately staged the axilla in male breast cancer patients and should be considered for axillary staging in male breast cancer patients with clinically negative axillae.

Sentinel lymph node biopsy in patients with multifocal breast cancer.

BACKGROUND: Multifocal or multicentric breast cancer has been suggested as a contraindication for sentinel node biopsy (SNB). However, recent studies have demonstrated that all quadrants of the breast drain through common afferent channels to a common axillary sentinel node. This should mean that the presence of multifocal tumour should not affect the lymphatic drainage. The purpose of this study was to evaluate the feasibility and accuracy of SNB in patients with multifocal breast cancer using a peritumoural injection technique for sentinel lymph node (SN) mapping. METHODS: In the ALMANAC multicentre trial validation phase, we took SNB samples from 842 patients with node negative, invasive breast cancer with use of a blue dye and radiolabelled colloid mapping technique at the peritumoural injection site. All patients underwent standard axillary treatment after SNB. Seventy-five of the 842 patients had multifocal lesions on final histopathologic examination. The following analysis is focused on patients with multifocal lesions. RESULTS: A mean number of 2.4 SNs were identified in 71 of 75 patients (identification rate: 94.7%). Thirty-one patients had a positive SN, 40 a negative SN. Standard axillary treatment confirmed the SN to be negative in 37 of 40 patients, whereas three patients revealed positive non-sentinel lymph nodes (false-negative rate: 8.8%). Overall SN biopsy accurately predicted axillary lymph node status in 68 of 71 patients (95.8%). CONCLUSION: SNB accurately staged the axilla in multifocal breast cancer and may become an alternative to complete axillary lymph node dissection in node negative patients with multifocal breast cancer.

High levels of allele loss at the FHIT and ATM genes in non-comedo ductal carcinoma in situ and grade I tubular invasive breast cancers.

Fifty-four grade 1 tubular breast cancers and nine non-comedo ductal carcinoma in situ samples have been analyzed for loss of heterozygosity using a series of microsatellite markers. Markers mapping to regions of the genome for which loss of heterozygosity has been documented previously in higher-grade breast cancers were selected for this analysis. Even within this group of good prognostic early breast cancers, genetic events are very common. The highest levels of loss were observed for D3S1300, which maps within an intron of the recently identified FHIT gene. High levels of loss were also observed within the ATM gene. These findings indicate that allele loss at FHIT and ATM may be an important early event in the development of sporadic breast cancer.

DNA fingerprinting of benign and malignant breast lesions.

Paired blood and breast tissue samples from 96 patients undergoing surgical excision of a breast lesion were subjected to DNA fingerprint analysis using the minisatellite probes 33.6 and 33.15. The 'fingerprints' of the blood and breast DNA were compared. DNA fingerprint changes seen were classified as band additions, band deletions or changes in band intensity. Significantly more DNA fingerprint changes were seen in malignant than in benign lesions (probe 33.6, P<0.01; probe 33.15, P=0.01; both probes, P = 0.04). The frequency of the changes detected in the breast cancers was unrelated to tumour grade or the presence of invasion. DNA ploidy was measured in 70 of the breast carcinomas. DNA fingerprint changes were seen in 41 of these, but flow cytometry detected aneuploidy in only 29 tumours (P=0.04). The DNA fingerprinting technique is unlikely to be useful in differentiating between benign and malignant breast lesions as changes were detected in one of the fibroadenomas studied. However, it may be a useful technique in screening tumour DNA for abnormalities suitable for more detailed analysis.

Ductal carcinoma in situ of the breast: correlation between mammographic and pathologic findings.

OBJECTIVE: Ductal carcinoma in situ shows heterogeneous clinical behavior and response to treatment depending on its pathologic features. The aim of this study was to correlate the radiologic and pathologic features of ductal carcinoma in situ of the breast. Differences, if present, may allow refinement of diagnosis and selection of treatment options. MATERIALS AND METHODS: The mammograms of 128 patients with ductal carcinoma in situ of the breast were analyzed by a radiologist who knew that the patients had ductal carcinoma in situ but had no other pathologic information. The radiologic and pathologic features of subgroups characterized according to cell size and presence of necrosis were then compared. Statistical comparisons were made by using the chi 2- and Fisher's exact tests. RESULTS: Patients with small-cell ductal carcinoma in situ more commonly have a normal mammogram (28% vs 6%, respectively, p < .001) or an abnormal mammogram without calcification (42% vs 5%, respectively, p < .001) than do patients with large-cell ductal carcinoma in situ. Among patients with abnormal mammographic findings, calcification is present in 58% of those with small-cell ductal carcinoma in situ, compared with 95% of those with large-cell ductal carcinoma in situ (p < .001). No significant differences were found in the calcification morphology of small- and large-cell ductal carcinoma in situ. These features were seen more commonly in ductal carcinoma in situ with necrosis than in ductal carcinoma in situ without necrosis, respectively: abnormal mammographic findings (95% vs 73%, p < .001), calcification (96% vs 61%, p < .001), calcification with a ductal distribution (80% vs 45%, p < .005), and rod-shaped calcification (83% vs 45%, p < .001). An abnormal mammogram without calcification (39% vs 4%, p < .001) or predominantly punctate calcification (36% vs 13%, p < .05) was seen more commonly in ductal carcinoma in situ without necrosis than in ductal carcinoma in situ with necrosis, respectively. CONCLUSION: We have shown that the radiologic features of ductal carcinoma in situ vary according to cell size and the presence of necrosis in particular. Necrosis has been found to be a feature of more biologically aggressive in situ breast cancer, so these findings may be of practical value in deciding the management of indeterminate calcification clusters and whether to offer breast conservation.

Screening-detected and symptomatic ductal carcinoma in situ: mammographic features with pathologic correlation.

PURPOSE: To compare the mammographic and pathologic features of screening-detected and symptomatic ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: The mammographic and pathologic features of 54 screening-detected and 77 symptomatic cases of DCIS were compared. Patients were aged 30-76 years (mean, 58 years). RESULTS: Diffuse involvement was seen in 10 patients (13%) with symptoms but in none of the screening-detected group (P < .05). The disease was radiologically more extensive in the symptomatic group. Calcifications in the symptomatic group (n = 48) were less likely to have a ductal distribution than those in the screening-detected group (n = 48) (30 [63%] vs 40 [83%], respectively; P < .05). At histologic examination in some cases, the symptomatic group (n = 76) included eight (11%) patients with cribriform-micropapillary, large-cell tumors (P < .05) and less comedocarcinoma (20 [26%] vs 23 [45%], respectively; P < .05) compared with the screening-detected group (n = 51). CONCLUSION: The results show differences in the radiologic and pathologic features of screening-detected and symptomatic DCIS.