Pathological prognostic factors in breast cancer.
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Breast Neoplasms↗
Biomedical subjects
S E Pinder
Publications and source records attributed to S E Pinder.
Microinvasive carcinoma of the breast: diagnostic criteria and clinical relevance.
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Breast Neoplasms↗
Is mammography of value in women with disseminated cancer of unknown origin?
Mammography is often requested to try to identify occult primary breast carcinoma in women with metastatic cancer of unknown primary site. This study aimed to investigate whether mammography is of use in these patients in identifying the breast as the origin of the metastatic disease. Thirty-one women with a working diagnosis of metastatic cancer underwent mammography in an attempt to determine the primary site. None of these women had a palpable breast mass. The site of presentation, pathological type of tumour, site of origin, and benefit of mammography and mammography-provoked biopsy were clarified for each patient. The patients were also followed up to determine survival. The commonest sites of presentation were lung (45%), lymph nodes (19%) and abdomen (16%). The primary sites of these cancers were identified with confidence in 27 patients (87%). The commonest known primary tumour sites were lung (45%), breast (16%) and ovary (16%). Abnormal mammograms were detected in four patients (13%), but three of these did not have breast cancer. In one, the site of origin remained indeterminate, as either breast or lung. Five (16%) had a confident diagnosis of breast carcinoma; all of these women had normal mammograms. We conclude that mammography in women presenting with metastatic disease from an unknown primary site is unhelpful and is not recommended. Furthermore, we could not demonstrate its value in women presenting with axillary lymphadenopathy.
Adult↗
A comparison of 14 and 12 gauge needles for core biopsy of suspicious mammographic calcification.
This study was carried out to compare the efficacy of 14 vs 12 G needles in stereotactic core biopsy of mammographic calcification. A consecutive series of 100 impalpable mammographic calcifications, without an associated mass and requiring stereotactic core biopsy were randomly allocated to either 14 G or 12 G needle sampling. All biopsies were performed using an upright stereotactic digital unit (Senovision GE) and a Bard automated biopsy gun. Core biopsy results were categorized as either normal, benign, atypical ductal hyperplasia, suspicious of ductal carcinoma in situ (DCIS), DCIS or invasive cancer. The radiographic calcification retrieval rates, complete and absolute sensitivity for malignancy of DCIS and DCIS with an invasive focus were obtained by comparison of core results with surgical histology. Radiographic calcification retrieval was achieved in 86% when using 14 G and 12 G needles. The absolute sensitivity and complete sensitivity for diagnosing DCIS were the same with 12 G and 14 G needles (72% versus 71% and 93% versus 94%, respectively). The use of 12 G needles does not appear to confer benefit over the use of 14 G needles in the diagnosis of mammographic calcification.
Biopsy, Needle↗
A critical appraisal of existing classification systems of epithelial hyperplasia and in situ neoplasia of the breast with proposals for future methods of categorization: where are we going?
Current classification systems for borderline lesions of the breast including epithelial hyperplasia, atypical hyperplasia, and ductal carcinoma in situ fall short of the ideal. They present pathologists with problems of recognition or clear distinction and clinicians with difficult management choices. In addition, recent evidence indicates that different pathogenetic lesions are present in some categories. This article presents a brief critical appraisal of the existing classifications and offers suggestions for revision using a model of pathogenetic lineage.
Breast↗
The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy.
BACKGROUND: Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single-center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies. METHODS: The authors assessed the value of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a multicenter, randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V). RESULTS: NHG was a predictor of overall survival for both LN negative and LN positive patients (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN negative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an increase of one grade resulted in a significant overall survival disadvantage regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observed difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater overall and disease free survival benefit from prolonged chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013, respectively); LN positive patients with Grade 1 or 2 disease in both treatment arms had comparable overall and disease free survival. A strong correlation between the previously utilized Bloom-Richardson grading system (BRG) and NHG was observed (P < 0.001 and kappa=82%) and no apparent differences in overall and disease free survival were observed between the two systems. NHG did, however, identify a greater proportion of tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3. CONCLUSIONS: This multicenter clinical study confirms the value of histologic grade, and the authors propose that this technique be used to identify Grade 3, LN positive patients who will benefit from prolonged rather than perioperative chemotherapy.
Antimetabolites, Antineoplastic↗
The accuracy of breast ultrasound in the evaluation of clinically benign discrete, symptomatic breast lumps.
INTRODUCTION: Recent reports have suggested that breast ultrasound (US) is of value in distinguishing malignant from benign processes. The aim of this study was to establish the accuracy of US in detecting invasive malignancy in clinically benign, discrete, symptomatic breast lumps. METHODS: The US appearances of 205 clinically benign breast masses were documented prospectively and prior to mammography by one radiologist (AJE). The US appearances were then correlated with the fine needle aspiration (FNA), core biopsy and surgical findings and compared with the mammographic findings. RESULTS: The US findings were normal 72 (35%), simple cyst 63 (31%), solid benign 51 (25%), solid indeterminate 15 (7%) and solid malignant four (2%). Ultrasound characterized 13 (93%) of the 14 patients found to have invasive carcinoma as indeterminate or malignant. No patients with normal or simple cyst US findings had invasive malignancy. Ultrasound had significantly better accuracy (97% vs 87%, P < 0.02) sensitivity (93% vs 57%, P < 0.05) and negative predictive value (99% vs 92%, P < 0.002) than mammography in the detection of invasive carcinoma when indeterminate and malignant imaging findings were taken as positive. CONCLUSION: US is a useful adjunct to FNA/core biopsy in confirming the nature of symptomatic, clinically benign breast masses and is superior to mammography in this clinical setting.
Adult↗
Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications: a comparative study with long follow-up.
The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening and the more widespread use of breast-conserving surgery have led to a search for histological features associated with the risk of recurrence. In a case control study of 141 patients with long follow-up, we compared the ability of five morphological classifications to predict recurrence after local excision. A significant correlation was not found between recurrence and growth pattern when a traditional classification based on architecture was used nor with necrosis when a scheme based principally on this feature was employed. A correlation was, however, found between recurrence and "differentiation" as defined by nuclear features and cell polarization in a classification recently formulated by the European Pathologists Working Group (EPWG), but this failed to reach statistical significance at the 5% level. A stronger and statistically significant correlation was found between nuclear grade as defined by the EPWG and recurrence when cell polarization was disregarded, using the classification currently employed by the UK National Health Service and European Commission-funded Breast Screening Programmes. This was attributable to a small number of recurring cases being downgraded as a consequence of exhibiting polarized cells. A significant correlation between histology and recurrence was also observed using the Van Nuys classification, which is based on nuclear grade and necrosis. Whether the tumor recurred as in situ or invasive carcinoma was unrelated to histological classification, as was the time course over which it occurred. These findings strongly support the use of nuclear grade to identify cases of DCIS at high risk of recurrence after local excision, but further work is necessary to determine whether nuclear grade or necrosis is more appropriate to subdivide the non-high-grade cases.
Adult↗
Prognostic factors in invasive carcinoma of the breast.
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Biomarkers↗
Fine needle aspiration (FNA) cytology of breast: refining the diagnosis.
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Adenoma, Pleomorphic↗
Fibroadenomatoid hyperplasia: a cause of suspicious microcalcification on mammographic screening.
OBJECTIVE: Fibroadenomatoid hyperplasia is a well-described but rare benign breast lesion with composite features of fibroadenoma and fibrocystic change. Because fibroadenomatoid hyperplasia has not to our knowledge been reported as a cause of suspicious microcalcifications and because several pathology reports of biopsies of mammographically detected microcalcification at our institution included fibroadenomatoid hyperplasia, we undertook this study to describe the features of mammographically detected microcalcification seen in patients with fibroadenomatoid hyperplasia. MATERIALS AND METHODS: Two breast pathologists reviewed the records of 54 mammographically detected lesions that were compatible with a diagnosis of fibroadenomatoid hyperplasia and that provoked subsequent core biopsy or surgical excision of microcalcifications. Eleven cases (20%) fulfilled the diagnostic criteria for fibroadenomatoid hyperplasia. The sites of all calcifications found at histology were documented, and the mammographic features were described. RESULTS: Eleven cases of fibroadenomatoid hyperplasia were identified in nine core biopsy samples and two surgical specimens. Calcification was present in all 11 pathologic specimens. Calcification was stromal in nine, subepithelial in two, and epithelial in none. The mammographic features of fibroadenomatoid hyperplasia in all 11 cases were granular microcalcifications that varied in shape, size, and density and had no associated mass; of these calcifications, 91% were in a localized, irregularly shaped cluster. Rod-shaped calcifications were also seen in 64% of cases. CONCLUSION: Fibroadenomatoid hyperplasia is a cause of suspicious, granular, clustered microcalcifications on screening mammography. Fibroadenomatoid hyperplasia can be confirmed using 14-gauge core biopsy in most cases.
Aged↗
Radiological features of papillary carcinoma of the breast.
Seventeen patients with papillary carcinoma of the breast were analysed with respect to the radiological findings by three experienced breast radiologists. The most frequent mammographic appearance of papillary tumours was of an ill-defined (70%) and lobulated (60%) mass and at ultrasound as a well-defined (76%), inhomogeneous (62%) and hypoechoic (92%) lesion. Histopathological subtypes of encysted papillary carcinoma, encysted papillary carcinoma with an invasive focus and invasive papillary carcinomas could not be predicted from the radiological features, although invasive tumours tended to be larger at presentation than the other subtypes.
Breast Neoplasms↗
Predictors of response to second-line endocrine therapy for breast cancer.
This study reports on factors predicting response to second-line endocrine therapy in 250 patients with breast cancer for which they were assessable for response by the International Union Against Cancer (UICC) criteria. Clinical details relating to first-line endocrine therapy were available for all patients. We have not included in this study patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy--e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, or remained in long-term remission on first-line endocrine therapy. One hundred and fifty nine patients (72%) achieved remission (objective response and static disease [OR + SD]) on first-line endocrine therapy with a median duration of 19 months. For second-line endocrine therapy the remission rate was 53% (132/225) with a median duration of 15 months. Tumour grade and oestrogen receptor status of the primary tumour were shown to be independent predictors of response to second-line endocrine therapy while response to first-line endocrine therapy was a predictor of the duration of response to second-line endocrine therapy. In the sub-group of patients who showed OR or SD to both first and second-line therapies, there was no correlation between the time to progression (TTP) on first and second-line therapies.
Adult↗
The detection of ductal carcinoma in situ at mammographic screening enables the diagnosis of small, grade 3 invasive tumours.
This study was carried out to assess the frequency of ductal carcinoma in situ (DCIS) occurring within and surrounding grade 3 invasive tumours and the effect of its detection on size and nodal stage of invasive carcinomas at mammographic detection. Grade 3 tumours with either no associated DCIS or DCIS only within the invasive component were significantly larger in size than tumours with surrounding DCIS (P < 0.02) and were less likely to be under or equal to 10 mm in size (0% or 13% vs 30% respectively, P < 0.02). Tumours with mammographic calcification were more likely to be less than or equal to 10 mm in size than non-calcific tumours (32% vs 11% respectively, P < 0.05). This was because of the high frequency of tumours less than or equal to 10 mm in size in the linear/branching calcification group. Tumours showing calcification without a mass also appear to be a group with good prognostic features, with a mean size of 13 mm, 33% being 10 mm or less in size and only 17% being node positive. We have found that the presence of surrounding DCIS enables earlier detection of grade 3 invasive carcinomas because of the presence of mammographically visible calcification. Detection of calcification suggestive of DCIS should remain an important part of mammographic screening.
Breast Neoplasms↗
Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates.
In an attempt to improve the quality of the breast FNA specimens we instigated a continuing audit of this procedure in this hospital. All FNAs since 1990 have had the following recorded: mode of aspiration, e.g. freehand or image guided, patient presentation (screening or symptomatic), patient diagnostic category, cytological diagnosis and final histological diagnosis. Aspirator performance was assessed by means of the inadequate aspiration rate (IR) of FNAs performed on patients with a final diagnosis of cancer (FDC) and diagnostic category A patients (clinically or radiologically malignant lesions). An ongoing annual review of the performance of all the aspirators was undertaken, all of whom received individual feedback. Counselling and further training were offered where indicated by poor performance. Over the period 1990-1995 a total of 13537 FNAs were performed by 27 aspirators. The IR on category A and FDC cases over this period was 16.0% and 18.1%. The best performance achieved by an aspirator in a calendar year was an IR of 3.6% with no inadequate specimens in either FDC or category A lesions, and the best performance over the entire period was an average IR of 11.75% and 14.25% for FDC and category A groups, respectively. The overall IR on category A patients ranged from 15.9% to 23.8% and on FDC cases from 12.2% to 21.7%. There was a significant improvement in individual junior aspirator performance when their first year was compared with their last year on the unit. In some cases a deterioration in intra-aspirator performance was observed, from an IR of 6% to 33%. The overall IR rate of the unit remained stable for FDC patients, 15.5% in 1990 compared with 15.1% in 1995. This appeared to be largely due to a high proportion of the aspirations being performed by experienced personnel with consistent IRs. However, concealed within the overall rate there were some poor performers who benefited from counselling and/or further training. These results indicate an important role for audit in identifying poor aspirators who benefit from targeted training and advice, thereby improving the quality of FNA specimens, and ultimately patient care.
Biopsy, Needle↗
The impact of core-biopsy on pre-operative diagnosis rate of screen detected breast cancers.
The UK breast screening Surgical Quality Assurance guidelines suggest a target for pre-operative diagnosis of screen detected cancer of over 70%. Core biopsy was introduced in our breast screening assessment clinics in April 1994 and this study reports the impact of introducing core biopsy on the pre-operative diagnosis rate. Between April 1994 and March 1995, 100 cancers were detected. Results of fine needle aspiration cytology and core biopsies were studied to assess the contribution of each to the pre-operative diagnosis rate of cancer and comparison made with results from the previous 2 years. After introducing core biopsy pre-operative diagnosis rates rose from 72% to 90% (P < 0.0002) leading to a 64% reduction in diagnostic biopsies for screen detected cancer. Malignant results were obtained in 61% of first FNA (similar to previous years) and 74% of first core biopsies (combined 87%). Repeat FNA/core diagnosed three further cancers increasing the final pre-operative diagnosis rate to 90%. Final pathological examination after surgical excision demonstrated an increase in the preoperative detection of DCIS from 39% to 82% (P < 0.01) and invasive disease from 80% to 92% (P < 0.02). The introduction of core biopsy has significantly improved our management of screen detected breast cancer.
Biopsy, Needle↗
Pure mucinous breast cancer-mammographic and ultrasound findings.
UNLABELLED: Aim to describe the mammographic and ultrasonographic features of pure mucinous breast cancer. PATIENTS AND METHODS: The mammographic features of 15 patients and ultrasonographic features of seven patients with pure mucinous breast cancer were reviewed retrospectively by three experienced breast radiologists. RESULTS: The commonest mammographic appearance was of a poorly defined (86%) lobulated (71%) mass which could contain calcification (14%). A well defined mass (14%) and suspicious calcifications without a mass (7%) were also seen. Ultrasound showed a mass lesion in all seven cases which was either hypoechoic (86%) or mixed echogenicity (14%); 86% had a heterogeneous internal echo pattern; 71% showed distal enhancement while none showed distal attenuation. CONCLUSION: The imaging features of pure mucinous cancer are different from more common types of breast carcinoma. It is possible to misinterpret the appearances of this slow growing tumour as a benign lesion due to rarity of speculation on mammography and distal attenuation on ultrasonography. Most cases do, however, show other features suggesting malignancy.
Adenocarcinoma, Mucinous↗
Is ipsilateral mammography worthwhile in Paget's disease of the breast?
AIMS: To identify the clinical value of pre-operative ipsilateral mammography in patients with Paget's disease of the breast. METHOD: The mammograms and histological data of 27 patients with Paget's disease and 60 patients with symptomatic DCIS without Paget's disease were reviewed and compared. RESULTS: Forty-four percent of patients with Paget's disease had normal mammograms. Mammography did not discriminate between DCIS and invasive disease, and could not predict DCIS sub-type. DCIS was large cell in 80% of patients with Paget's disease. Given that large cell DCIS in non Paget's patients is normally visible mammographically, the large proportion of Paget's patients with normal mammography is difficult to explain, but could be due to the small size of the lesions. Comparison of the Paget's and non-Paget's groups showed that large cell solid disease was more common, small cell cribriform less common and normal mammography more common in the Paget's group. Given that mastectomy is the treatment of choice, the only clinical value of ipsilateral mammography in our unit would be to allow image guided core biopsy of any detected mammographic abnormalities to determine the presence of invasive disease prior to surgery, thus indicating the need for node sampling pre-operatively rather than as a delayed procedure. This study also confirms that mammography is of little help in deciding if breast conserving surgery is appropriate for individual cases of Paget's disease of the nipple due to the insensitivity of mammography in showing the site of disease.
Adult↗