Is clinical breast examination important for breast cancer detection?

BackgroundScreening clinical breast examination (cbe) is controversial; the use of cbe is declining not only as a screening tool, but also as a diagnostic tool. In the present study, we aimed to assess the value of cbe in breast cancer detection in a tertiary care centre for breast diseases.MethodsThis retrospective study of all breast cancers diagnosed between July 1999 and December 2010 at our centre categorized cases according to the mean of detection (cbe, mammography, or both). A cbe was considered “abnormal” in the presence of a mass, nipple discharge, skin or nipple retraction, edema, erythema, peau d’orange, or ulcers.ResultsDuring the study period, a complete dataset was available for 6333 treated primary breast cancers. Cancer types were ductal carcinoma in situ (15.3%), invasive ductal carcinoma (75.7%), invasive lobular carcinoma (9.0%), or others (2.2%). Of the 6333 cancers, 36.5% (n = 2312) were detected by mammography alone, 54.8% (n = 3470) by mammography and cbe, and 8.7% (n = 551) by physician-performed cbe alone (or 5.3% if considering ultrasonography). Invasive tumours diagnosed by cbe alone were more often triple-negative, her2-positive, node-positive, and larger than those diagnosed by mammography alone (p < 0.05).ConclusionsA significant number of cancers would have been missed if cbe had not been performed. Compared with cancers detected by mammography alone, those detected by cbe had more aggressive features. Clinical breast examination is a very low-cost test that could improve the detection of breast cancer and could prompt breast ultrasonography in the case of a negative mammogram.     

Minimal access breast surgery – A single breast incision for breast conservation surgery and sentinel lymph node biopsy

Aims

Minimal access breast surgery (MABS) is a procedure that completes breast conservation surgery (BCS) and sentinel node biopsy (SNB) through a single incision. It allows access to axillary sentinel nodes via the breast incision and also provides access to the internal mammary nodes (IMN) as well as other nodal sites when needed. The aims of this study are to describe the MABS approach and to evaluate its safety and efficacy in cases undergoing BCS and SNB (axillary or IMN) for treatment of breast cancer.

Methods

The surgical technique for MABS is described. One hundred and three consecutive clinically lymph node negative patients undergoing BCS and SNB (axillary or IMN) were considered for MABS. Cases were classified according to the location of sentinel nodes dissected (axillary, internal mammary or other), the location of the tumour and whether MABS was used. The success of MABS was calculated based on the number of cases where BCS and SNB were completed through a single breast incision. Number of lymph nodes (LN) retrieved, rate of LN positivity, aesthetics and complications were documented.

Results

Eighty-six percent of cases of BCS with axillary-only SNB were completed with MABS. For cases of BCS with axillary and IMN SNB, MABS was successful for BCS and IMN SNB in 97% of cases and for BCS and SNB from both nodal regions in 63%. There was only one case, a woman with breast prostheses, who required three separate incisions. When axillary-only SNB cases were completed with MABS, an average of 2.9 axillary LN per case with a 29% axillary LN positivity rate was seen. When axillary and IMN SNB were completed with MABS for both regions, an average of 3.0 axillary LN per case were retrieved with an axillary LN positivity rate of 65%. When separate axillary and breast incisions were made, 2.7 LN per case were removed with an axillary LN positivity rate of 30%. Aesthetics were excellent and there were no complications associated with reaching the nodes through the breast incision.

Conclusion

MABS is a feasible option for the majority of women undergoing BCS and SNB and it does not compromise the success of SNB.     

Does breast cancer grade worsen with time? Evidence from breast screening

It has been suggested that alteration of the distribution of histological grades, that has been found in screening programmes, is evidence for progression in histological grade with increasing size. A predictive model, that was based upon estimated growth data from an unselected series of 98 new primary breast cancers, is used to estimate the proportions of tumors that would be diagnosed according to limiting screen diagnostic and clinical diagnostic sizes after particular screening intervals; windows of opportunity are created. The results show that the limitations imposed by time and size criteria alter the distribution of growth rates of tumours that may appear in the windows. Small screen diagnostic sizes and short screening intervals allow only the most rapidly growing tumours to reach large sizes. This produces an apparent association of grade 3 tumours with large size. Interval cancers are also likely to be more rapidly growing while the more slowly growing tumours will be diagnosed at the subsequent screen to produce a spurious association of slowly growing grade 1 tumours with small size. We conclude that the evidence from screening does not support the thesis of progression of histological grade with the ageing of the tumour, since the changes that have been observed are predictable from a simple model based upon patterns of tumour growth rates and the relationships between growth rate and histology.     

Lobular breast cancer: how useful is breast magnetic resonance imaging?

RATIONALE AND OBJECTIVES: To review magnetic resonance imaging (MRI) findings in lobular breast carcinoma, the in situ or infiltrating subtype, with special attention to the dynamic curves with the aim to evaluate possible differences with ductal carcinoma. METHODS: In 2 years, 27 patients with lobular and one with tubular carcinoma underwent MRI at the Istituto Nazionale Tumori of Milan. RESULTS: All lobular carcinomas demonstrated early or late enhancement (100% sensitivity), without significant differences in morphology compared with ductal carcinoma, but frequently with a different shape of the dynamic curves. CONCLUSIONS: Due to its infiltrative growth associated to only limited connective tissue reaction, lobular carcinoma often encounters difficulties in mammographic diagnosis. In contrast, MRI can be very helpful in evaluating the true extension of the disease, especially when breast conservation is considered. Due to a more consistent fibrotic stroma, these lesions sometimes show a delayed enhancement, which suggests that more than one set of subtracted images should be evaluated during MRI analysis.     

More breast cancer genes?

A new gene associated with a high risk of breast cancer, termed BRCAX, may exist on chromosome 13q. Tumours from multicase Nordic breast cancer families, in which mutations in BRCA1 and BRCA2 had been excluded, were analyzed using comparative genomic hybridization in order to identify a region of interest, which was apparently confirmed and refined using linkage analysis on an independent sample. The present commentary discusses this work. It also asks why there should exist genetic variants associated with susceptibility to breast cancer other than mutations in BRCA1 and BRCA2, and what might be their modes of inheritance, allele frequencies and risks. Replication studies will be needed to clarify whether there really is a tumour suppressor gene other than BRCA2 on chromosome 13q.     

Does multicentric/multifocal breast cancer differ from unifocal breast cancer? An analysis of survival and contralateral breast cancer incidence

Purpose we evaluated whether patients with multifocal/multicentric (M/M) breast cancer have different outcomes compared to unifocal (U) disease in terms of survival and the development of contralateral breast cancer (CBC) disease. Methods women diagnosed with stage I–III breast cancer were classified as having U or M/M disease. Prognostic factors were prospectively collected and obtained from the breast cancer outcome unit database. Univariate and multivariable analyses for the incidence of CBC were performed as well as Kaplan–Meier plots. Results 25,320 women met inclusion criteria. The 5-year cumulative incidence of CBC in the U versus M/M group was 2.3% (95% CI 2.1, 2.5) versus 2.4% (95% CI 1.6, 3.4) (P = 0.349). Breast cancer specific survival (BCSS) rate revealed a slightly worse outcome with M/M disease, RR = 1.174 (95% CI 1,004, 1.372). Conclusions M/M breast cancer did not increase the risk of metachronous CBC, but was associated with inferior BCSS.     

Is breast compression associated with breast cancer detection and other early performance measures in a population-based breast cancer screening program?

Purpose

We aimed to investigate early performance measures in a population-based breast cancer screening program stratified by compression force and pressure at the time of mammographic screening examination. Early performance measures included recall rate, rates of screen-detected and interval breast cancers, positive predictive value of recall (PPV), sensitivity, specificity, and histopathologic characteristics of screen-detected and interval breast cancers.

Methods

Information on 261,641 mammographic examinations from 93,444 subsequently screened women was used for analyses. The study period was 2007–2015. Compression force and pressure were categorized using tertiles as low, medium, or high. χ ² test, t tests, and test for trend were used to examine differences between early performance measures across categories of compression force and pressure. We applied generalized estimating equations to identify the odds ratios (OR) of screen-detected or interval breast cancer associated with compression force and pressure, adjusting for fibroglandular and/or breast volume and age.

Results

The recall rate decreased, while PPV and specificity increased with increasing compression force (p for trend <0.05 for all). The recall rate increased, while rate of screen-detected cancer, PPV, sensitivity, and specificity decreased with increasing compression pressure (p for trend <0.05 for all). High compression pressure was associated with higher odds of interval breast cancer compared with low compression pressure (1.89; 95% CI 1.43–2.48).

Conclusions

High compression force and low compression pressure were associated with more favorable early performance measures in the screening program.

     

Does resection of an intact breast primary improve survival in metastatic breast cancer?

The recommended primary treatment approach for women with metastatic breast cancer and an intact primary tumor is the use of systemic therapy. Local therapy of the primary tumor is recommended only for palliation of symptoms. However, a series of retrospective studies examining practice patterns for this problem show that about half the women presenting with de novo metastatic disease undergo resection of the primary tumor, and suggest that women so treated survive longer than those who do not undergo resection of the intact primary. In analyses that adjust for tumor burden (number of metastatic sites), types of metastases (visceral, nonvisceral), and the use of systemic therapy, the hazard ratio for death is reduced by 40% to 50% in women receiving surgical treatment of the primary tumor. The benefit of surgical treatment appears to be confined to women whose tumors were resected with free margins. However, these results may simply reflect a selection bias (ie, younger, healthier women with a smaller tumor burden are more likely to receive surgical treatment). In addition, the role of other locoregional therapy such as axillary dissection and radiotherapy is not addressed in these studies. In view of these data, the role of local therapy in women with stage IV breast cancer needs to be reevaluated, and local therapy plus systemic therapy should be compared to systemic therapy alone in a randomized trial.     

Is breast cancer ever cured? Follow-up study of 5623 breast cancer patients.

The authors evaluated 5623 cases of primary breast cancer followed for 1 to 21 years. Overall and breast cancer death rates were determined and compared to expected rates. Breast cancer patients showed overall and breast cancer death rates significantly higher than expected and which persisted at long-term follow-up. The observed/expected overall death ratios for follow-up periods of 0-5, 6-10, 11-15 or 16-20 years were 3.61, 2.55, 1.60 and 2.11, respectively. Death rates from breast cancer at 5, 10, 15 and 20 years were 20%, 32%, 40% and 48% respectively. The evidence of a persistent excess mortality even after long-term follow-up suggests the hypothesis that breast cancer is a systemic disease when clinically diagnosed. This study provided no evidence of a "clinical" cure for breast cancer patients. Even for N- patients the 5, 10, 15 and 20 year death rates from breast cancer were 12%, 20%, 28% and 38%, respectively. N- breast cancer, which is currently considered as a localized disease cured by surgery in most cases, would be better regarded to as a slow-growing metastatic disease, although "personal" cure may be achieved in many subjects dying of causes other than breast cancer.     

Screening clinical breast examination: how often does it miss lethal breast cancer?

BACKGROUND: Although most American women regularly receive screening clinical breast examination (CBE), little is known about CBE accuracy in community practice. We sought to estimate the rate of cancer detection (sensitivity) of screening CBE performed by community-based clinicians on women who ultimately died of breast cancer, as well as to identify factors associated with accurate detection. SUBJECTS AND METHODS: We evaluated CBE accuracy among asymptomatic female health plan enrollees in five states (WA, OR, CA, MA, and MN) who received a CBE within 1 year of breast cancer diagnosis and who died of breast cancer within 15 years of diagnosis (N = 485). Sensitivity was estimated as the proportion whose exam was abnormal. Bivariate and logistic regression analyses identified patient characteristics associated with cancer detection. RESULTS: An abnormality was noted on screening CBE in one of five women who ultimately succumbed to breast cancer (sensitivity = 21.6%; 95% confidence interval [CI] = 18.1% to 25.6%). The odds of a true-positive screening CBE (sensitivity) were decreased among women using estrogen (odds ratio [OR] = 0.23; 95% CI = 0.07 to 0.80), receiving a Pap smear during the same visit as CBE (OR = 0.45; 95% CI = 0.27 to 0.72), and with increasing chronic disease comorbidity (P(trend) = .08). CONCLUSION: Screening CBE as performed in the community may be insufficiently sensitive to detect most lethal breast cancers. Low sensitivity of screening CBE in community practice may be partly attributable to its performance alongside time-consuming clinical tasks such as Pap smear screening or chronic illness care.     

Ductal carcinoma in situ of the breast: is breast conserving treatment feasible?

Between 1968 and 1993, 43 cases of ductal carcinoma in situ of the breast (DCIS) were treated. We examined the extent of the cancer using multiple sections of surgical specimens and considered whether or not breast conserving treatment (BCT) is feasible for treatment of DCIS. In nine out of 40 patients (23%), extent of the cancer was classified as grade III, defined as extension over a 2.5-cm margin around the tumor. Among those nine cases, 67% (6/9) had extensive microcalcification on mammography. With respect to the correlation between the tumor size and the extent of the cancer, 29%(5/17) of the cases with a small size tumor, ie, 1.0 cm or less, showed grade III or greater. All tumors with a size of 1.1-2.0 cm showed grade II or lower, and 50%(4/8) of cases with a tumor size of 2.1 cm or more showed grade III or greater. Concerning the relationship between the histological subtype and the extent of the cancer, 22%(2/9) of comedo carcinomas and 23%(7/30) of noncomedo carcinomas showed grade III or greater. The histological extent thus showed no difference between comedo carcinoma and noncomedo carcinoma. It follows that, when BCT performed on DCIS consists of lumpectomy alone, BCT is feasible when the tumor size is 1.1-2.0 cm. without extensive microcalcification on mammography. However, BCT for comedo carcinoma should be approached with caution because of its malignant behavior, although there was no difference in histological extent between comedo and noncomedo carcinoma.     

Multiple foci of invasive breast cancer: can breast MRI influence surgical management?

The use of MRI to assess the extent of breast disease is gaining increasing popularity with the subsequent detection of multiple invasive foci within the breast that had not been identified on previous standard mammography and ultrasonography. What impact this has on subsequent surgical management and ultimately disease-free survival remains a controversial topic. Should histologically confirmed multiple foci of invasive disease within a breast steer the surgical management towards mastectomy, or is there a role in select patients for breast conserving surgery, even if two or more incisions are required? This review considers the evidence for how MRI affects the mastectomy rate and compares this to surgical outcomes for breast conserving surgery in the presence of multiple invasive foci.     

Evolution of breast cancer therapeutics: Breast tumour kinase’s role in breast cancer and hope for breast tumour kinase targeted therapy

There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients’ overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase (Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current “state of play” with respect to targeted therapy for breast cancer, as well as discussing Brk’s role in the processes underlying tumour development and metastasis and its potential as a therapeutic target in breast cancer.     

Is clinical breast examination effective in Japan? Consideration from the age-specific performance of breast cancer screening combining mammography with clinical breast examination

Background

There is controversy about the value of clinical breast examination (CBE) in breast cancer screening programs that include mammography.

Methods

In Fukui Prefecture, a screening combining mammography with CBE was employed on 62,447 women from 2004 to 2009. We examined the sensitivity and specificity of mammography alone, and mammography and CBE together for each age group (40–49, 50–59, 60–69, and 70–79).

Results

167 breast cancers and 49 false-negative cancers were detected during 5 years. For the combined screening, the sensitivities were 73.1, 74.1, 78.3, and 86.5 %, and the specificities were 83.8, 87.5, 89.8, and 90.9 % in the groups of 40–49, 50–59, 60–69, and 70–79 years, respectively. In the mammography-specific analysis, sensitivity decreased to 69.8 % (?3.3 %), 66.7 % (?7.7 %), 77.3 % (?1.0 %), and 83.8 % (?2.7 %) in the groups of 40–49, 50–59, 60–69, and 70–79 years, respectively. There were greater reductions in the groups of 40–49 and 50–59 years than in those of 60–69 and 70–79 years, but there was no statistically significant decrease. Specificity generally increased with increasing age and there was a significant improvement in specificity among all age groups, except that of 70–79 years.

Conclusions

Our findings suggest that there is a trade-off between sensitivity and specificity associated with CBE added to mammography. This tendency is greater in those 40–50 years of age than in those 60–70 years of age. We consider that CBE may be omitted from breast cancer screening among women aged 60 and 70 years. Furthermore, another modality to complement mammography screening in younger Japanese women is expected.

     

How safe is oncoplastic breast conservation?: Comparative analysis with standard breast conserving surgery

Aim

Oncoplastic techniques are increasingly used to facilitate breast conservation and maintain breast aesthetics but evidence with regards to the oncological safety of oncoplastic breast conservation surgery (oBCS) remains limited. The aim of this study was to compare re-excision and local recurrence rates for oBCS with standard breast conserving surgery (sBCS).

Methods

From June 2003 to Feb 2010 data was obtained from contemporaneously recorded electronic patient records on patients who had oBCS and sBCS within a single breast cancer centre. Re-excision rates and local recurrence rates were compared.

Results

A total of 440 sBCS and 150 oBCS (in 146 women) were included in this study. Median tumour size and specimen weight was 21 mm and 67 g for oBCS and 18 mm and 40 g in the sBCS group (p < 0.001). Re-excision was 2.7% (4/150) and 13.4% (59/440) for oBCS and sBCS respectively (p < 0.001). At a median follow-up of 28 months, local relapse was 2.7% (4) and 2.2% (10) and distant relapse 1.3% (2) and 7.5% (33) for oBCS and sBCS respectively.

Conclusions

Oncoplastic breast conserving techniques decrease re-excision rates. Early follow up data suggests oncological outcomes of oncoplastic breast conservation surgery are similar to standard breast conservation.