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S E Pinder

Publications and source records attributed to S E Pinder.

At least 73 records · Page 4Linked to original sources
PubMed2001

Prognostic and predictive factors in primary breast cancer and their role in patient management: The Nottingham Breast Team.

Breast cancer is the most common carcinoma amongst women in the Western world, yet there are now encouraging signs that improvements in mortality may be a realistic target. Increasing breast awareness amongst women due to better health education can lead to earlier clinical detection. In addition, population screening with mammography can achieve a significant improvement in survival. With significant changes in the range and type of therapeutic options available for patients with breast cancer, there is now a trend towards patients exercising their right in management and therapeutic decisions. All these developments highlight the increasing importance of prognostic and predictive factors in the management of patients with breast cancer. In this review we will discuss current prognostic and predictive factors with particular emphasis on those of relevance in routine histopathology, especially with respect to their clinical applications.

Adult↗
PubMed2001

Preoperative assessment of prognostic factors in breast cancer.

The adoption of preoperative diagnostic strategies involving fine needle aspiration cytology (FNAC) or core biopsy is well established, allowing the planning of operating lists and bed occupancy and patient involvement in therapeutic management. In addition to diagnosis, however, pathologists are increasingly being asked to provide pathological prognostic information from preoperative samples. This leader describes techniques for predicting prognosis and response to treatment on these specimens and some of the problems inherent in the determination of prognosis on small samples. For example, although histological grade can be assessed relatively reliably on either core or FNAC samples, the evaluation of tumour type (which includes an overall assessment of the architecture of a given tumour) may be less reliable on small preoperative samples. Other well recognised histological prognostic factors, such as vascular channel invasion or tumour size, cannot be determined accurately on small preoperative samples. For those patients who might benefit from neoadjuvant treatment, predicting the response to such treatments--for example, by the assessment of oestrogen receptor status--can readily be performed on either core biopsy or FNAC. In the future, other molecular markers such as C-erbB-2 might also prove beneficial in predicting response to newly developed treatments.

Biomarkers, Tumor↗
PubMed2001

Detecting which invasive cancers at mammographic screening saves lives?

OBJECTIVES: Assessment of the features of primary operable breast carcinomas arising in women known to subsequently develop metastatic disease, to show for which invasive breast cancers earlier detection by mammographic screening is potentially beneficial. These data were applied to a separate series of screen detected cancers. METHODS: Features associated with the development of metastatic disease after a previous operable breast cancer were ascertained from examination of histological sections of the initial primary carcinoma and in particular the incidence of nodal positivity and definite vascular invasion. Trends in the frequency of nodal involvement and vascular invasion according to histological grade, invasive size, and tumour type were then examined in a further group of 573 screen detected invasive cancers to predict the likelihood of development of systemic disease in these women. RESULTS: Of 173 women who developed metastatic disease after a previous operable breast cancer, 79 (72%) had nodal metastases and 62 (59%) had definite vascular invasion. A high proportion (84%) had either lymph node metastases or vascular invasion or both. The absence of vascular invasion and nodal involvement in invasive breast cancer indicated a low risk of subsequent development of metastatic disease. In the screen detected group, grade 1 invasive cancers <20 mm in size and grade 2 and 3 cancers <10 mm in size had low rates of nodal involvement and vascular invasion. There was a gradual trend to small size, lymph node negativity, and less vascular invasion when comparing screen detected ductal carcinoma of no special type, tubular mixed carcinoma, and tubular carcinoma. Cancers with a lobular component tended to be larger and more often lymph node positive than ductal and no specific type carcinomas. CONCLUSIONS: These data suggest that identification of grade 1 cancers less than 20 mm in size and grade 2 and 3 cancers less than 10 mm in size at screening is likely to be beneficial, with a lower likelihood of developing metastatic disease from these lesions. The detection of tubular mixed carcinomas and ductal carcinomas of no specific type also appears beneficial. However the detection of tumours with lobular features at breast screening does not seem to significantly benefit the patient.

Breast Neoplasms↗
PubMed2001

Screen detected ductal carcinoma in situ (DCIS): overdiagnosis or an obligate precursor of invasive disease?

OBJECTIVES: Ductal carcinoma in situ (DCIS) represents 20%-25% of malignancy detected at mammographic screening. This study aims to clarify the value of detecting DCIS at mammographic screening by assessing its biological characteristics and by comparing screen detected DCIS with a series of symptomatic DCIS lesions. METHODS: 222 Screen detected and 151 symptomatic cases of pure DCIS were identified. Their histological grade and the prevalence of necrosis were ascertained and compared. RESULTS: Of the screen detected lesions 28 (13%) were low grade, 40 (18%) intermediate grade, and 153 (69%) high grade. Of screen detected lesions 186 (87%) were necrotic and 29 (13%) were not. Of the 151 symptomatic lesions 24 (16%) were low grade, 34 (23%) intermediate grade, and 89 (61%) high grade. Of symptomatic lesions 112 (75%) were necrotic and 36 (24%) were not necrotic. Screen detected DCIS was more often necrotic (p=0.008) than symptomatic DCIS. CONCLUSIONS: As most DCIS detected at screening is high grade and necrotic, aggressive investigation of suspicious microcalcification at mammographic screening is advocated. Given the biological features of screen detected DCIS, the existence of an upper limit for the detection of DCIS by the NHS breast screening programme seems to be inappropriate.

Adult↗
PubMed2000

Breast cancer diagnosis using scattered X-rays.

Small-angle X-ray diffraction data has been collected from 99 ;core-cut' breast tissue specimens representing a number of different pathologies. Data in the range 75-1390 A have been compared with controls from patients with no breast disease. Bessel functions and Bragg maxima resulting from the fibrillar structure of collagen have been identified. The Bragg maxima indexed onto a 649 A lattice. Systematic differences in the intensities and D-spacings between the collagen of malignant, benign and normal tissue groups have been clearly demonstrated and quantified. These differences appear to be due to a significantly lower structural order within the malignant tissues. Possible explanations for this are discussed and the potential for utilizing this observation in cancer diagnosis is considered.

Journal Article↗
PubMed2000

Gamma linolenic acid with tamoxifen as primary therapy in breast cancer.

Gamma linolenic acid (GLA) has been proposed as a valuable new cancer therapy having selective anti-tumour properties with negligible systemic toxicity. Proposed mechanisms of action include modulation of steroid hormone receptors. We have investigated the effects of GLA with primary hormone therapy in an endocrine-sensitive cancer. Thirty-eight breast cancer patients (20 elderly Stage I-II, 14 locally advanced, 4 metastatic) took 8 capsules of oral GLA/day (total = 2.8 g) in addition to tamoxifen 20 mg od (T+GLA). Quality and duration of response were compared with matched controls receiving tamoxifen 20 mg od alone (n = 47). Serial tumour biopsies were taken to assess changes in oestrogen receptor (ER) and bcl-2 expression during treatment. GLA was well tolerated with no major side effects. T+GLA cases achieved a significantly faster clinical response (objective response vs. static disease) than tamoxifen controls, evident by 6 weeks on treatment (p = 0.010). There was significant reduction in ER expression in both treatment arms with T+GLA objective responders sustaining greater ER fall than tamoxifen counterparts (6-week biopsy p = 0.026; 6-month biopsy p = 0.019). We propose GLA as a useful adjunct to primary tamoxifen in endocrine-sensitive breast cancer. The effects of GLA on ER function and the apparent enhancement of tamoxifen-induced ER down-regulation by GLA require further investigation.

Administration, Oral↗
PubMed2000

Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement.

In the histologic grading of invasive breast cancer with the Nottingham modification of the Scarff-Bloom-Richardson grading scheme (NSBR), it has been found that when pathologists disagree, they tend not to disagree by much. However, if tumor grade is to be used as an important parameter in making treatment decisions, then even this generally small degree of pathologist variability in assessing grade needs to be correlated with patient outcome. Findings from the Nottingham/Tenovus Primary Breast Cancer Study were used for patient outcome data. Kaplan-Meier survival curves were constructed for NSBR scores grouped according to the level at which pathologists tend to agree in assessing grade, from a reproducibility perspective. For example, if a given tumor were assessed by several pathologists as having either an NSBR score of 5 or 6, then what is the correct score--the intermediate-grade Score 6 assessments or the low-grade Score 5 assessments? By "regrouping" the Nottingham outcome data such that data from patients with Score 5 tumors are grouped with patients having Score 6 tumors (a 5-6 group), then the level in which the pathologists agreed with each other (that the tumor was either score 5 or 6) is better matched with patient outcome. In response to the above example, it was not surprising to find that patients with Score 5-6 tumors had a probability of survival between the established low and intermediate NSBR final combined grades. However, it is the discussion of this approach that highlights that optimal use of grading requires awareness of the level of pathologist agreement and understanding the value of pathologists' reaching consensus in assessments. Also, knowledge of possible clinical decision thresholds can help in providing relevant interpretations of grading results.

Adenocarcinoma↗
PubMed2000

Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases.

AIMS: This study presents a series of five cases in which metaplastic carcinoma, predominantly low-grade adenosquamous carcinoma, of the breast is seen arising within a background of a complex sclerosing lesion. This association has been recognized previously but has not been documented in detail. This study describes the characteristics of the components present in each case and discusses the existing literature. This observation adds further evidence to support an association between some types of invasive breast carcinoma and sclerosing lesions of the breast. METHODS AND RESULTS: Four of these cases were received as referral cases for opinion. The fifth was received as part of the routine surgical workload within our own institution. Two patients presented following mammographic screening and three symptomatically; their mean age was 62 years (range 49-68). The mean lesion size was 16 mm (range 7-24). All five lesions showed features of a complex sclerosing lesion/radial scar in the form of central sclerosis with elastosis and radiating benign entrapped tubules. One had associated benign papillary structures and two had focal benign squamous metaplasia. Four cases showed coexisting but distinct areas of low-grade adenosquamous carcinoma with glandular and squamous epithelial differentiation in a spindle cell background. One case had associated undifferentiated spindle cell carcinoma. Detailed immunophenotypic characteristics of two cases are presented. CONCLUSIONS: This series illustrates a postulated but previously unconfirmed association between an unusual form of metaplastic breast carcinoma (adenosquamous carcinoma) and complex sclerosing lesions. The mechanisms of induction of breast carcinoma are poorly understood but these observations further emphasize the potential for sclerosing lesion of the breast to be associated with, and possibly give rise to, invasive carcinoma of different types. The precise nature of the interaction between the pathological processes remains unclear.

Aged↗
PubMed2000

When have mammographic calcifications been adequately sampled at needle core biopsy?

AIMS: To determine if the number of flecks of calcification retrieved at stereotaxic core needle biopsy or the number of core samples obtained containing calcification are related to biopsy sensitivity, and to determine how many calcifications or cores containing calcification the radiologist should aim to retrieve when sampling mammographic microcalcification. MATERIALS AND METHODS: A retrospective review was performed of core specimen radiographs from 57 consecutive patients who had stereotaxic core needle biopsies of impalpable malignant microcalcifications without an associated mammographic mass. The total number of calcifications retrieved and the numbers of cores containing calcification were correlated with findings at core and surgical histology. RESULTS: Increasing retrieval of calcification elements visible on specimen radiography was associated with increasing sensitivity of the biopsy. Five or more flecks of calcium gave an absolute sensitivity of 100%. Increasing numbers of core samples obtained containing radiographically demonstrable calcification was also associated with increasing sensitivity. Three or more cores containing calcium resulted in a 100% absolute sensitivity for malignancy. CONCLUSION: To ensure adequate sampling of calcification at core biopsy, an optimum of either three or more cores containing calcium or five or more flecks of calcium in total is required. Achieving this target ensures a high pre-operative diagnosis rate for malignant microcalcifications.Bagnall, M. J. C. (2000). Clinical Radiology 55, 548-553.

Aged↗
PubMed2000

Ultrasound guided core biopsy of suspicious mammographic calcifications using high frequency and power Doppler ultrasound.

AIM: The pre-operative diagnosis of suspicious mammographic microcalcifications usually requires stereotactic needle biopsy. The aim of this study was to evaluate if high frequency 13 MHz ultrasound (HFUS) and power Doppler (PD) can aid visualization and biopsy of microcalcifications. MATERIALS AND METHODS: Forty-four consecutive patients presenting with microcalcifications without associated mammographic or palpable masses were examined with HFUS and PD. Ultrasound-guided core biopsy (USCB) was performed where possible. Stereotactic biopsy was carried out when US-guided biopsy was unsuccessful. Surgery was performed if a diagnosis of malignancy was made on core biopsy or if the repeat core biopsy was non-diagnostic. RESULTS: Forty-one patients (93%) had ultrasound abnormalities corresponding to mammographic calcification. USCB was performed on 37 patients. In 29/37, USCB obtained a definitive result (78.4%). USCB was non-diagnostic in 4/9 benign (44.4%) and 4/28 (14.3%) malignant lesions biopsied. The complete and absolute sensitivities for malignancy using USCB were 85.7% (24/28) and 81% (23/28), respectively. USCB correctly identified invasive disease in 12/23 (52.2%) cases. There was no significant difference in the presence of abnormal flow on PD between benign and malignant lesions. However, abnormal PD vascularity was present in 43.5% of invasive cancer and was useful in directing successful biopsy in eight cases. CONCLUSION: The combination of high frequency US with PD is useful in the detection and guidance of successful needle biopsy of microcalcifications particularly where there is an invasive focus within larger areas of DCIS.

Biopsy, Needle↗
PubMed2000

Digital imaging improves upright stereotactic core biopsy of mammographic microcalcifications.

AIM: This comparative study was carried out to assess the effect of using digital images compared to conventional film-screen mammography on the accuracy of core biopsy of microcalcifications using upright stereotactic equipment. MATERIALS AND METHODS: The biopsy results from a consecutive series of 104 upright stereotactic 14-gauge core biopsies performed with conventional X-ray (Group A) were compared with 40 biopsies carried out using stereotaxis with digital imaging (Group B). In all cases specimen radiography was performed and analysed for the presence of calcifications. Pathological correlation was then carried out with needle and surgical histology. RESULTS: The use of digital add-on equipment increased the radiographic calcification retrieval rate from 55 to 85% (P < 0.005). The absolute sensitivity of core biopsy in pure ductal carcinoma in situ (DCIS) cases rose from 34 to 69% (P < 0.03), with the complete sensitivity increasing from 52 to 94% (P < 0.005). For DCIS with or without an invasive component the absolute sensitivity rose from 41 to 67% (P = 0.052), while the complete sensitivity was 59% before and 86% after the introduction of digital imaging (P < 0.04). CONCLUSION: Digital equipment improves the performance of upright stereotactic core biopsy of microcalcifications, giving a significantly increased success rate in accurately obtaining calcifications. This leads to an improvement in absolute and complete sensitivity of core biopsy when diagnosing DCIS.

Adult↗
PubMed2000

c-erbB-4 protein expression in human breast cancer.

The Type 1 family of growth factor receptors includes epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4. Overexpression of the first two members is associated with poorer prognosis in patients with breast carcinoma. In this study we examined the expression of c-erbB-4 protein using the monoclonal antibody HFR-1. A total of 127 consecutive cases of primary operable invasive breast carcinoma presenting between 1975 and 1977 were studied. All patients were managed by simple mastectomy or conservation surgery with radiotherapy and no adjuvant therapy given. Long-term follow-up was maintained. Routine, formalin-fixed, paraffin-embedded tumour samples were used and sections were stained immunohistochemically using the Duet StreptABC method. Immunoreactivity was classified using a simple semi-quantitative scoring method. Protein expression was generally low but definite positive cytoplasmic, membranous and nuclear reactivity was identified in 58%, 41% and 25% of cases respectively. Expression at all three sites demonstrated significant inverse associations were histological grade. In addition, membrane accentuation correlated inversely with the Nottingham Prognostic Index (NPI), while cytoplasmic reactivity showed a positive association with c-erbB-3 expression. No significant associations were found with disease-free interval or survival. The results of this study demonstrate that higher levels of c-erbB-4 protein expression are associated with a more differentiated histological phenotype in contrast to the other members of the Type 1 family. Larger series with extended follow-up will be required to ascertain definitively the prognostic value of c-erbB-4 expression in breast carcinoma.

Adult↗
PubMed1999

Endocrine response and resistance in breast cancer: a role for the transcription factor Fos.

We have previously demonstrated that elevated Fos expression may be important in de novo endocrine resistance in breast cancer. However, changes in Fos expression during endocrine response and subsequently on acquisition of resistance are unknown. This study immunocytochemically monitors Fos protein within sequential biopsies from primary human breast cancer patients obtained pre-treatment (T1), during tamoxifen therapy (T2, T3) and on disease progression (T5), examining in parallel proliferation [i.e., MIBI (Ki67) immunostaining, mitotic activity], cellularity and endocrine response. Significantly diminished Fos, proliferation and cellularity were observed after 6 weeks of therapy in patients exhibiting a better quality and/or duration of response, while modest Fos increases and a maintained proliferation and cellularity were seen in poorer responders. Decreases in Fos, proliferation and cellularity at 6 months similarly hallmarked better responders. We confirmed a significant association between de novo resistance and elevated Fos and proliferation. Additionally, however, these parameters increased at the time of disease relapse over pre-treatment and "on therapy" values. Our data indicate that tamoxifen response involves a reduction in both tumor cell proliferation and cell survival, potentially entailing diminished Fos protein expression in better-responding patients. Our data are also supportive of elevated Fos expression being involved in the departure from endocrine control inherent in both primary and acquired resistance.

Aged↗
PubMed1999

An immunohistochemical examination of the expression of E-cadherin, alpha- and beta/gamma-catenins, and alpha2- and beta1-integrins in invasive breast cancer.

This study examines the expression of the cell-cell adhesion molecules E-cadherin and its associated proteins, the catenins and the matrix-cell adhesion molecules beta1- and alpha2-integrins, in primary invasive breast carcinoma. Expression was assessed immunohistochemically on frozen sections by semi-quantitative scoring of the intensity and proportion of immunoreactivity in 55 cases. Associations with each other and with other histological and prognostic features and survival were sought. There was a significant association between loss of E-cadherin expression and loss of alpha- and beta/gamma-catenin immunostaining. In 20 per cent of cases, membranous immunoreactivity with E-cadherin antibody was absent. Absent cytoplasmic expression of alpha- and beta/gamma-catenins was seen in 24 and 22 per cent of breast cancers, respectively. The intensity of reactivity with E-cadherin showed a significant association with histological grade (p=0.002) and tumour type (p<0.001). Lobular carcinomas frequently showed loss of expression of E-cadherin, as reported elsewhere; loss of catenin expression was also found in these tumours. alpha-catenin intensity also showed a relationship with grade (p=0.008) and with oestrogen receptor (ER) status (p=0.006). beta/gamma-catenin expression was not associated with other known prognostic factors. Forty-nine per cent and 42 per cent of cases showed no membrane immunostaining with beta1- and alpha2-integrin, respectively, and co-ordinated loss of beta1- and alpha2-integrin expression was found. Both beta1- and alpha2-integrin expression were associated with histological grade (p=0.003 and p=0.031, respectively) and beta1 immunoreactivity with tumour type (p=0.010). None of the variables examined showed a statistically significant association with tumour size or lymph node stage, or with overall survival, although a trend was seen (p=0.087) towards poorer survival of patients with tumours with absent or weak expression of beta1-integrin. The expression of these markers is of biological interest, but appears to be of little additional use in predicting clinical behaviour.

Adult↗
PubMed1999

Bilateral breast carcinomas: do they have similar mammographic features?

AIMS: This study compared the mammographic appearance, site and histological features of synchronous and metachronous bilateral breast carcinomas. METHODS: Site, type of abnormality and background pattern seen on the diagnostic mammograms of 63 women with bilateral breast carcinoma were compared. The histological type and grade of all the carcinomas were verified by histological review. RESULTS: There was a tendency for the contralateral tumour to have similar mammographic features to those of the initial tumour. In patients in whom the first carcinoma was visible purely as a mass, the contralateral carcinoma had a similar appearance in 82% (P < 0.001). When the original tumour showed mammographic calcification the contralateral tumour did so in 65% (P< 0.001). Normal mammography or calcification alone were seen almost exclusively in women with a dense background pattern (100% and 92% respectively) while masses and calcification with masses were seen in women with dense and fatty patterns (58% and 35% dense respectively). When the mammographic site of the contralateral tumour was compared with that of the first tumour no significant correlation could be demonstrated. There was a significant trend for contralateral carcinomas to be of the same histological grade (P < 0.005) but not histological type. CONCLUSIONS: Contralateral carcinomas often have a similar mammographic appearance to the first tumours. Two factors may be responsible: (i) the tendency for contralateral carcinomas to be of the same histological grade and (ii) the influence of mammographic background pattern on the radiological appearance of breast carcinoma. This knowledge may assist in the interpretation of follow-up mammography in patients with a previous breast carcinoma.

Adult↗
PubMed1999

Mammographic features of ductal carcinoma in situ (DCIS) present on previous mammography.

AIM: To review previous mammograms of women found later to have DCIS and identify features which may have been missed or misinterpreted as benign. METHODS: The previous mammograms of 50 women who developed DCIS were analysed. The mammographic features at diagnosis and on the prior mammograms were compared. RESULTS: 11 (22%) of the previous mammograms were in retrospect abnormal; 5 (45%) of these had previously been assessed for the abnormality. All showed microcalcification. The following features were commoner at diagnosis than on previous films; rod shaped calcification (64 vs. 27%, P = 0.03) and a ductal distribution of calcification (76 vs. 45%, P = 0.05). Predominantly punctate calcification (64 vs. 12%, P = 0.001) and less than 10 calcifications in the cluster (54 vs. 24%, P = 0.05) were more common on the previous films. No difference was found in the frequency of granular calcification, branching calcification, irregularity in density, size or shape of calcification between the two groups. CONCLUSION: Features of DCIS missed on previous mammography include small cluster size, less than 10 calcifications in the cluster, the absence of rod shaped calcifications, the absence of a ductal distribution and the presence of predominantly punctate calcification. Features frequently seen both at diagnosis and on previous films which might have allowed earlier diagnosis were granular calcifications which vary in size, density and shape in an irregularly shaped cluster. Focal clustered calcification deserves aggressive investigation.

Adult↗