MR-guided vacuum-assisted breast biopsy: is it an essential technique?

Background  In the United States and Europe, MR-guided vacuum-assisted biopsy (VAB) is required for MR-only visible suspicious lesions that cannot be identified with mammography or ultrasonography. However, it is controversial as to whether MR-guided VAB is essential or not in Japan. The purpose of this study was to clarify the frequency of malignancy among the patients that underwent MR-guided VAB, and to discuss the need for this technique in Japan. Methods  This study was approved by the Institutional Review Board of our hospital. A retrospective review was performed of 30 consecutive patients who had undergone MR-guided 11-gauge VAB. The biopsies were performed on a 1.5 T MR scanner using a commercially available biopsy system. All lesions seen with MRI could not be detected by mammography and second-look ultrasonography. Results  All 30 lesions were assessed as category 4 or 5. The average lesion size of a mass enhancement before biopsy was 0.7 cm, and the average lesion size of a non-mass-like enhancement was 2.3 cm. The average number of cores of VAB was 19. The median time required to perform the VAB procedure was 35 min. The biopsy was successfully performed without important side effects in all patients. Histopathological findings were invasive ductal carcinoma in one (3%); ductal carcinoma in situ (DCIS) in seven (23%); and benign in 22 (73%). In one case, atypical ductal hyperplasia at VAB was upgraded to DCIS at surgical excision. Conclusion  MR-guided VAB can be performed safely and it is needed for MR-only visible suspicious lesions in Japan.     

Outcome of MRI-guided vacuum-assisted breast biopsy – initial experience at Institute of Oncology Ljubljana,Slovenia

Background

Like all breast imaging modalities MRI has limited specificity and the positive predictive value for lesions detected by MRI alone ranges between 15 and 50%. MRI guided procedures (needle biopsy, presurgical localisation) are mandatory for suspicious findings visible only at MRI, with potential influence on therapeutic decision. The aim of this retrospective study was to evaluate our initial clinical experience with MRI-guided vacuum-assisted breast biopsy as an alternative to surgical excision and to investigate the outcome of MRI-guided breast biopsy as a function of the MRI features of the lesions.

Patients and methods.

In 14 women (median age 51 years) with 14 MRI-detected lesions, MRI-guided vacuum-assisted breast biopsy was performed. We evaluated the MRI findings that led to biopsy and we investigated the core and postoperative histology results and follow-up data.

Results

The biopsy was technically successful in 14 (93%) of 15 women. Of 14 biopsies in 14 women, core histology revealed 6 malignant (6/14, 43%), 6 benign (6/14, 43%) and 2 high-risk (2/14, 14%) lesions. Among the 6 cancer 3 were invasive and 3 were ductal carcinoma in situ (DCIS). The probability of malignancy in our experience was higher for non-mass lesion type and for washout and plateau kinetics.

Conclusions

Our initial experience confirms that MRI-guided vacuum-assisted biopsy is fast, safe and accurate alternative to surgical biopsy for breast lesions detected at MRI only.     

Low Rates of Additional Cancer Detection by Magnetic Resonance Imaging in Newly Diagnosed Breast Cancer Patients Who Undergo Preoperative Mammography and Ultrasonography

Purpose

We evaluated the efficacy of breast magnetic resonance imaging (MRI) for detecting additional malignancies in breast cancer patients newly diagnosed by breast ultrasonography and mammography.

Methods

We retrospectively reviewed the records of 1,038 breast cancer patients who underwent preoperative mammography, bilateral breast ultrasonography, and subsequent breast MRI between August 2007 and December 2010 at single institution in Korea. MRI-detected additional lesions were defined as those lesions detected by breast MRI that were previously undetected by mammography and ultrasonography and which would otherwise have not been identified.

Results

Among the 1,038 cases, 228 additional lesions (22.0%) and 30 additional malignancies (2.9%) were detected by breast MRI. Of these 228 lesions, 109 were suspected to be malignant (Breast Imaging-Reporting and Data System category 4 or 5) on breast MRI and second-look ultrasonography and 30 were pathologically confirmed to be malignant (13.2%). Of these 30 lesions, 21 were ipsilateral to the main lesion and nine were contralateral. Fourteen lesions were in situ carcinomas and 16 were invasive carcinomas. The positive predictive value of breast MRI was 27.5% (30/109). No clinicopathological factors were significantly associated with additional malignant foci.

Conclusion

Breast MRI was useful in detecting additional malignancy in a small number of patients who underwent ultrasonography and mammography.     

The Clinical Utility of Automated Breast Volume Scanner: A Pilot Study of 139 Cases

Purpose

The aim of this study is to evaluate the clinical utility of automated breast volume scanner (ABVS) for detecting and diagnosing the breast lesions.

Methods

From December 2010 to January 2012, bilateral whole breast examinations were performed with ABVS for 139 women. Based on the Breast Imaging Reporting and Data System (BI-RADS) categories, the breast lesions were evaluated on coronal multiplanar reconstruction images using the ABVS workstation. Then, the imaging results were compared with those on conventional handheld ultrasound (HHUS) images. Histological diagnoses were performed on BI-RADS category 4 and 5 lesions.

Results

A total of 453 lesions were detected by ABVS. On the HHUS, 33 new lesions were detected but 69 lesions were not detected. BI-RADS category 2 and 3 matched to those on ABVS at 73.5% (61/83) and 85.4% (276/323). In 47 lesions of BI-RADS category 4 or 5, there was an exact match to those on ABVS. In addition, 47 lesions were classified as BI-RADS category 4 and 5, for which an ultrasound-guided core needle biopsy was performed. The malignant lesions of BI-RADS category 4 and 5 showed the following: 2/27 (7.4%) in 4A, 4/5 (80%) in 4B, 2/2 (100%) in 4C, and 13/13 (100%) in 5. The ABVS showed 21 true positives and a positive predictive value of 44.7% (21/47).

Conclusion

There was considerable agreement in the assessment of the breast lesions by ABVS and HHUS. The ABVS had advantages of high diagnostic accuracy, examiner-independence, multislice visualization of the whole breast and less time-consuming. Our results indicate that ABVS might be a useful modality in diagnosing breast lesions.     

Incidental Breast Lesions Identified by 18F-FDG PET/CT: Which Clinical Variables Differentiate between Benign and Malignant Breast Lesions?

Purpose

The aim of our study was to evaluate the risk of malignancy and to determine which clinical variables differentiate between benign and malignant focal breast lesions found incidentally on ¹⁸F-flourodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT).

Methods

From March 2005 to October 2011, 21,224 women with no history of breast cancer underwent FDG PET/CT at three university-affiliated hospitals. We retrospectively identified 214 patients with incidental focal hypermetabolic breast lesions and grouped them into benign and malignant lesion groups. Of the 214 patients, 82 patients with 91 lesions were included in this study. All lesions were confirmed histologically or were assessed by follow-up imaging for greater than 2 years. The patient age, maximum standardized uptake value (SUV_max), lesion size on ultrasonography (US), and Breast Imaging-Reporting and Data System (BI-RADS) category on US in conjunction with mammography were compared between the groups. Multivariate logistic regression analysis was used to identify independent factors associated with malignancy.

Results

The risk of malignancy was 29.7% (27/91) in breast incidentalomas detected by FDG PET/CT. The univariate analysis showed that the patient age, SUV_max, tumor size, and BI-RADS category differed significantly between the malignant and benign groups. The multivariate analysis showed that the BI-RADS category was the only significant factor differentiating benign from malignant lesions (p=0.002).

Conclusion

BIRADS category based on US in conjunction with mammography was the only useful tool to differentiate between malignant and benign lesions in breast incidentalomas on FDG PET/CT.     

Synchronous BI-RADS Category 3 Lesions on Preoperative Ultrasonography in Patients with Breast Cancer: Is Short-Term Follow-Up Appropriate?

Purpose

Breast ultrasonography (US) has been widely used in the preoperative examination of patients with breast cancer. Breast Imaging Reporting and Data System (BI-RADS) category 3 (C3) lesions (probably benign) are regarded as having a low probability of malignancy (≤2%). The purposes of this study were to verify the malignancy rates for synchronous BI-RADS C3 lesions in patients with breast cancer and consider appropriate management strategies for these lesions.

Methods

Between January 2010 and January 2013, a total of 161 patients underwent surgery in our institute for breast cancer and synchronous BI-RADS C3 lesions. In the US reports, we found records of 219 synchronous BI-RADS C3 nodules in 161 patients. They were excised during surgery for breast cancer management. Stepwise logistic regression analysis was used to identify predictors of malignancy for synchronous BI-RADS C3 lesions.

Results

The rate of malignancy among the 219 BI-RADS C3 lesions was 9.6%. In simple logistic regression analysis, the size of the primary tumor (p<0.001), pathologic T (pT) stage (p=0.002), and progesterone receptor (PR) status of the primary tumor (p=0.029) were significant predictive factors. In multiple logistic regression analysis, the pT stage and PR status of the primary tumor remained significant predictors (p=0.004 and p=0.003, respectively), and human epidermal growth factor receptor 2 (HER2) was identified as another significant factor (p=0.006).

Conclusion

In patients with breast cancer who are scheduled for surgery, needle biopsy or excision should be considered for synchronous BI-RADS C3 lesions identified on preoperative US when the primary tumor has the following risk factors: large size, high PR expression, and HER2 positivity.     

Follow-up of benign screen-detected breast lesions with suspicious preoperative needle biopsies

Aim

To study the outcome of patients with screen-detected breast lesions in whom preoperative core biopsy (CB), or fine needle aspiration cytology (FNAC), or both were suspicious of malignancy or malignant, but the final histology of the excised lesion was benign.

Materials and methods

Thirty-nine patients who fulfilled the above criteria were identified from a prospectively entered database of 192,153 breast screening examinations at the Bedfordshire and Hertfordshire Breast Screening Unit. Thirty-four patients had suspicious or malignant preoperative FNAC and/or CB, and five had FNAC only. Follow-up was mainly by mammograms. Outcome data were collected from hospital case notes and radiology reports.

Results

The median follow-up period was 3 years following excision biopsy. One patient whose excision biopsy histology was atypical ductal hyperplasia developed a mammographically occult carcinoma in the same breast after 24 months. There were no other cancers reported during this time.

Conclusion

The problem of suspicious preoperative needle biopsies with benign excision biopsy is uncommon in the breast screening population. These patients are not at an increased risk of being diagnosed with a carcinoma in the subsequent 3 years and may be discharged back to standard breast screening.     

Incidence and possible pathogenesis of sentinel node micrometastases in ductal carcinoma in situ of the breast detected using molecular whole lymph node assay

Background:

The pathogenesis of lymph node metastases in preinvasive breast cancer – ductal carcinoma in situ (DCIS) – remains controversial. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can assess a whole node and detect clinically relevant metastases. In this retrospective cohort study, we determined the performance of the OSNA assay in DCIS and the pathogenesis of node-positive DCIS.

Methods:

The subjects consisted of 623 patients with DCIS who underwent sentinel lymph node (SN) biopsy. Of these, 2-mm-sectioned nodes were examined using frozen-section (FS) histology in 338 patients between 2007 and 2009, while 285 underwent OSNA whole node assays between 2009 and 2011. The SN-positivity rate was compared between cohorts, and the characteristics of OSNA-positive DCIS were investigated.

Results:

The OSNA detected more cases of SN metastases than FS histology (12 out of 285, 4.2% vs 1 out of 338, 0.3%). Most of the metastases were micrometastases. The characteristics of high-risk DCIS (i.e., mass formation, size, grade, and comedo) and preoperative breast biopsy (i.e., methods or time to surgery) were not valid for OSNA assay–positive DCIS.

Conclusion:

The OSNA detects more SN metastases in DCIS than FS histology. Further examination of the primary tumours and follow-up of node-positive DCIS are needed to elucidate the pathogenesis.     

Human papilloma virus is associated with breast cancer

Background:

There is increasing evidence that high-risk human papilloma virus (HPV) is involved in cancers in addition to cervical cancer. For example, it is generally accepted that HPV has a role in a significant proportion of head and neck tumours, and it has long been hypothesised that hormone dependent oncogenic viruses, such as HPV may have causal roles in some human breast cancers. A number of reports have identified HPV DNA in breast tissue and breast cancer specimens, but these rely on standard polymerase chain reaction (PCR), which is criticised for its propensity for contamination.

Methods:

We have used two different technologies, in situ and standard PCR (with sequencing), and histology based on light microscopy.

Results:

We unambiguously demonstrate the presence of high-risk HPV in the cells of breast cancer specimens and breast cancer cell lines. In addition, we also show that the oncogenic characteristics of HPV associated breast cancer are very similar to HPV-associated cervical cancer. Specifically, that putative koilocytes are present in some HPV associated breast cancers.

Interpretation:

The above observations indicate a likely causal role for high-risk HPV in human breast cancer and offer the possibility of primary prevention of some breast cancers by vaccination against HPV.     

Clinical Outcome of Magnetic Resonance Imaging-Detected Additional Lesions in Breast Cancer Patients

Purpose

The aim of this study was to investigate the clinical outcome of additional breast lesions identified with breast magnetic resonance imaging (MRI) in breast cancer patients.

Methods

A total of 153 patients who underwent breast MRI between July 2006 and March 2008 were retrospectively reviewed. Thirty-three patients (21.6&) were recommended for second-look ultrasound (US) for further characterization of additional lesions detected on breast MRI and these patients constituted our study population.

Results

Assessment for lesions detected on breast MRI consisted of the following: 25 benign lesions (73.5&), two indeterminate (5.9%), and seven malignant (20.6%) in 33 patients. Second-look US identified 12 additional lesions in 34 lesions (35.3%) and these lesions were confirmed by histological examination. Of the 12 lesions found in the 11 patients, six (50.0%) including one contralateral breast cancer were malignant. The surgical plan was altered in 18.2% (six of 33) of the patients. The use of breast MRI justified a change in treatment for four patients (66.7%) and caused two patients (33.3&) to undergo unwarranted additional surgical procedures.

Conclusion

Breast MRI identified additional multifocal or contralateral cancer which was not detected initially on conventional imaging in breast cancer patients. Breast MRI has become an indispensable modality in conjunction with conventional modalities for preoperative evaluation of patients with operable breast cancer.     

High frequency of complex TP53 mutations in CNS metastases from breast cancer

Background:

Brain metastasis from breast cancer is usually associated with a poor prognosis and early death. Alteration of p53 may contribute to malignant progression by abrogation of apoptosis induced by oncogene activation and by acquisition of gain-of-function properties, which promote tumour aggression. Mutation in TP53 occurs at high frequency in carcinomas of the lung and gastro-intestinal tract, but is much less frequent, at 25%, in primary breast cancer. The frequency of TP53 alteration in the central nervous system (CNS) metastatic breast cancer is not known.

Methods:

In all, 23 cases of histologically confirmed CNS metastatic breast cancer were identified and the coding sequence of TP53 determined. TP53 was also sequenced in two control series of primary breast carcinomas from independent clinical centres.

Results:

We demonstrate a strikingly high frequency of TP53 mutation in the CNS metastatic lesions with an over-representation of complex mutations (non-sense/deletions/insertions). Complex mutations occur in metastatic lesions in both triple-negative breast cancer and hormone receptor/HER2-positive cases. Analysis of paired primary carcinomas and brain metastatic lesions revealed evidence for both clonal selection and generation of new mutations (missense and complex) in progression from a primary breast carcinoma to brain metastasis.

Conclusion:

Mutation in TP53 is the most common genetic alteration reported during metastasis to the brain in breast cancer.     

The Evaluation of Contralateral Breast Lesions in Breast Cancer Patients Using Reduction Mammoplasty

Purpose

This study evaluated the importance of routine pathological examination of contralateral breast specimens in breast cancer patients using reduction mammoplasty.

Methods

The weight of breast tissue resected from the contralateral breast in 71 patients and the number of slices used for pathological evaluation were recorded. Breast lesions found in the contralateral breast and accompanying lesions with tumors were examined.

Results

High risk proliferative lesions were reported in the contralateral breast of eight (11.2%) patients, and low-risk lesions were detected in 18 (25%). While the mean age of the patients with high-risk lesions was 45.6, it was 52.8 for the other patients (p=0.036).

Conclusion

Bilateral reduction mammoplasty may be beneficial to delineate some pathologies in contralateral breasts even in those patients with normal clinical and radiological findings. The incidental discovery of these pathologies is much more likely in young breast cancer patients.     

Use of Core Needle Biopsy rather than Fine-Needle Aspiration Cytology in the Diagnostic Approach of Breast Cancer

Background and Aims

In the following study case, we reviewed breast ultrasound-guided core needle biopsy (CNB), using Mammotome (vacuum-assisted breast biopsy) and Tru-cut, carried out on palpable and nonpalpable uncertain breast lumps or malignant large lesions to be submitted to neoadjuvant chemotherapy.

Material and Methods

Examinations were conducted during a 4-year period of clinical activity in a highly specialized center, from December 2009 to December 2013, in 712 patients previously subjected to fine-needle aspiration cytology (FNAC).

Results

The results demonstrated that among the 712 breast biopsies, in many cases FNAC was not conclusive, and therefore we proceeded with the echo-guided biopsy, through which we were able to collect sufficient material for the histological examination in order to direct patients to surgery or follow-up.

Conclusions

CNB is far superior to FNAC, especially in cases of uncertainty, where it is preferable to proceed directly with CNB, which may also determine additional prognostic and predictive markers. Initially FNAC is less expensive, but the actual costs involved tend to be higher for FNAC as it is less accurate and a CNB is often required. In accordance with recent publications, we can confirm the full validity of CNB in the diagnostic approach of breast lesions.Key words: Core needle biopsy, Fine-needle aspiration cytology, Breast cancer prevention     

Risk of breast cancer associated with papilloma

Objective

The purpose of this study was to investigate the risk of carcinoma in patients with a diagnosis of papilloma of the breast made on ultrasound large core biopsy or stereotactic vacuum-assisted biopsies.

Material and methods

This retrospective database review (2000–2007) included 130 patients with a papilloma diagnosed on preoperative biopsies or excisional surgery specimen. The mean patient age was 52 years (range, 20–80 years). The examinations included mammography and ultrasonography in all 130 patients. The final surgical histology was compared to preoperative biopsy diagnosis, and then factors associated with underestimation of malignancy were evaluated in univariate and multivariate analyses.

Results

The preoperative histology was available for 63 patients. Benign papilloma had been identified by ductography in 34 patients and by preoperative biopsy in 48 patients. Mammography showed microcalcifications in 25 cases and nipple discharge was present in 59 patients. Malignancy was found on final histology in 8% of patients with initial diagnosis of benign papilloma. In this study group, age of more than 50 years, presence of nipple discharge and microcalcifications were found to be significantly related to the risk of malignancy (p = 0.001, 0.05 and 0.02, respectively).

Conclusion

Since benign papilloma can be associated to malignancy at excisional biopsy, we still recommend surgical excision for papilloma especially when associated to identified risk factors of malignancy.     

Atypical phimosis secondary to a preputial metastasis from rectal carcinoma

Background

Cutaneous metastases from colorectal cancer are uncommon, accounting for 6.5% of all secondary skin lesions. They occur in advanced disease. The most common site is the abdomen. The penis is a rare site.

Case Report

We report the case of a 79-year-old patient who presented, two years after rectocolectomy for a rectal adenocarcinoma, obstructive renal failure secondary to a presacral recurrence, as well as symptomatic phimosis associated with papulonodules invading the penis, scrotum and pubis. After hemodialysis, percutaneous pyelostomy, and double-J catheter placement, the patient underwent circumcision and a pubic skin biopsy. On histology and immunohistochemistry, a cutaneous metastasis originating from the rectal adenocarcinoma was diagnosed.

Conclusions

Penile invasion by colorectal cancer revealed by phimosis is a rare occurrence but needs to be recognized and promptly diagnosed by biopsy in order to propose appropriate adjuvant therapy. These rare lesions can occur without any liver or lung involvement.Key words: Colorectal cancer, Phimosis, Penile metastasis, Cutaneous metastasis     

Breast Angiosarcoma: Case Series and Expression of Vascular Endothelial Growth Factor

Purpose

Angiosarcoma of the breast is a rare, malignant tumor for which little is known regarding prognostic indicators and optimal therapeutic regimens. To address this issue, we performed a retrospective analysis of breast angiosarcoma cases seen at Stanford University along with immunohistochemical analysis for markers of angiogenesis.

Methods

Breast angiosarcoma cases seen between 1980 and 2008 were examined. Viable tissue blocks were analyzed for expression of vascular endothelial growth factor and its receptors.

Results

A total of 16 cases were identified. Data was collected regarding epidemiology, treatment, response rates, disease-free survival, and the use of various imaging modalities. Five tissue blocks remained viable for immunohistochemical analysis. Vascular endothelial growth factor-A was positively expressed in 3 of these samples.

Conclusion

Angiosarcoma of the breast is an aggressive malignancy with a propensity for both local recurrence and distant metastases. Angiogenesis inhibition may represent a novel therapeutic modality in this rare, vascular malignancy.Key Words: Breast, Angiosarcoma, Vascular, Endothelial, Angiogenesis     

Breast lesions in reduction mammaplasty specimens: a histopathological pattern in 534 patients

Background:

The prevalence of breast lesions (benign, precancerous and cancer lesions) in reduction mammaplasty (RM) specimens has rarely been reported in Europe and never in the Swiss population.

Methods:

Personal and histopathological data from 534 female patients who underwent RM were reviewed.

Results:

Benign and/or malignant lesions were detected in 76.2% of all patients. Benign breast lesions associated with an increased risk of developing breast cancer represented 2.8% of all lesions. Breast cancer in situ was identified in 5 (0.9%) patients. Patient age and previous history of breast cancer were risk factors for incidental breast cancer.

Conclusion:

The rate of incidental carcinoma in situ was higher for patients with breast cancer history. Probably due to preoperative breast cancer investigation, no occult invasive breast cancer was found in reduction mammary specimens. Therefore before RM, breast cancer evaluation should be considered for all patients, especially for those with breast cancer risk factors (e.g., patient age, personal history of breast cancer).     

Independent predictors of breast malignancy in screen-detected microcalcifications: biopsy results in 2545 cases

Background:

Mammographic microcalcifications are associated with many benign lesions, ductal carcinoma in situ (DCIS) and invasive cancer. Careful assessment criteria are required to minimise benign biopsies while optimising cancer diagnosis. We wished to evaluate the assessment outcomes of microcalcifications biopsied in the setting of population-based breast cancer screening.

Methods:

Between January 1992 and December 2007, cases biopsied in which microcalcifications were the only imaging abnormality were included. Patient demographics, imaging features and final histology were subjected to statistical analysis to determine independent predictors of malignancy.

Results:

In all, 2545 lesions, with a mean diameter of 21.8 mm (s.d. 23.8 mm) and observed in patients with a mean age of 57.7 years (s.d. 8.4 years), were included. Using the grading system adopted by the RANZCR, the grade was 3 in 47.7% 4 in 28.3% and 5 in 24.0%. After assessment, 1220 lesions (47.9%) were malignant (809 DCIS only, 411 DCIS with invasive cancer) and 1325 (52.1%) were non-malignant, including 122 (4.8%) premalignant lesions (lobular carcinoma in situ, atypical lobular hyperplasia and atypical ductal hyperplasia). Only 30.9% of the DCIS was of low grade.Mammographic extent of microcalcifications >15 mm, imaging grade, their pattern of distribution, presence of a palpable mass and detection after the first screening episode showed significant univariate associations with malignancy. On multivariate modeling imaging grade, mammographic extent of microcalcifications >15 mm, palpable mass and screening episode were retained as independent predictors of malignancy. Radiological grade had the largest effect with lesions of grade 4 and 5 being 2.2 and 3.3 times more likely to be malignant, respectively, than grade 3 lesions.

Conclusion:

The radiological grading scheme used throughout Australia and parts of Europe is validated as a useful system of stratifying microcalcifications into groups with significantly different risks of malignancy. Biopsy assessment of appropriately selected microcalcifications is an effective method of detecting invasive breast cancer and DCIS, particularly of non-low-grade subtypes.     

Mitochondrial D310 mutations in the early development of breast cancer

Background:

The role of mitochondrial DNA (mtDNA) mutations in the development of breast cancer is largely unknown. In this study, we investigated the frequency and pattern of mutations in the D310 region, the most commonly mutated region in mtDNA, in a series of breast lesions.

Methods:

Using capillary electrophoresis, we genotyped the D310 sequence of neoplastic epithelial cells from 23 patients with synchronous ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), 26 patients with IDC only and 29 patients with DCIS only.

Results:

A majority of DCIS (68.4%) and IDC (71.4%) lesions harbour different D310 sequences compared with their matched normal control. Specific D310 sequences were more frequently identified in tumour samples (77.1% of DCIS and 75.5% of IDC) compared with normal tissues (35.3% of normal; P<0.0001). No difference was identified between DCIS lesions with synchronous IDC and those from pure DCIS cases. In five cases, histologically normal tissue adjacent to tumour was found to share D310 sequences with the tumour, while normal tissue taken further away did not.

Conclusion:

Although D310 alterations do not seem to be related to DCIS progression, they were found in histologically normal cells adjacent to tumour. This suggests a field of genetically altered cells, thus D310 mutations could represent a potential marker for the clonal expansion of premalignant breast cancer cells.