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Biomedical subjects

A D Baildam

Publications and source records attributed to A D Baildam.

At least 19 recordsLinked to original sources
PubMed2006

Effects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations.

There is considerable interest in whether anti-oestrogens can be used to prevent breast cancer in women bearing mutations in the BRCA1 and BRCA2 genes. The effects of oestradiol (E2), tamoxifen (TAM) and fulvestrant (FUL) on proliferation and steroid receptor expression were assessed in normal breast epithelium taken from women at varying risks of breast cancer and implanted into athymic nude mice, which were treated with E2 in the presence and absence of TAM or FUL. Tissue samples were taken at various time points thereafter for assessment of proliferative activity and expression of oestrogen and progesterone receptors (ERalpha and PgR) by immunohistochemistry. Oestradiol increased proliferation in the breast epithelium from women carrying mutations in the BRCA1/2 genes, those otherwise at increased risk and those at population risk of breast cancer. This increase was reduced by both TAM and FUL in all risk groups. In the absence of E2, PgR expression was reduced in all risk groups but significantly more so in the BRCA-mutated groups. Subsequent E2 treatment caused a rapid, complete induction of PgR expression in the population-risk group but not in the high-risk or BRCA-mutated groups in which PgR induction was significantly delayed. These data suggest that the mechanisms by which E2 induces breast epithelial PgR expression are impaired in BRCA1/2 mutation carriers, whereas those regulating proliferation remain intact. We conclude that early anti-oestrogen treatment should prevent breast cancer in very high-risk women.

Adolescent↗
PubMed2003

Management of accessory breast tissue in the axilla.

BACKGROUND: Accessory breasts occur in 0.4-6 per cent of women. They may be asymptomatic or cause pain, restriction of arm movement, cosmetic problems or anxiety. It is currently recommended that all accessory breasts be removed surgically but complications following this procedure have been poorly documented. METHODS: All patients who presented with axillary accessory breasts between July 1999 and October 2000 were identified from a computer database. A retrospective review of patients listed for excision of accessory breast tissue was undertaken to determine any postoperative complications. RESULTS: Women with axillary accessory breasts represented 0.5 per cent of all new referrals. A total of 28 women (80 per cent of those diagnosed) had surgery. Eleven patients experienced postoperative complications; the majority followed operations performed by a trainee. CONCLUSION: Excision of accessory axillary breast tissue was associated with significant morbidity.

Axilla↗
PubMed2003

Long term results of a randomised prospective study of preservation of the intercostobrachial nerve.

AIM: We have previously reported in a randomised controlled trial comparing intercostobrachial nerve (ICBN) preservation with division that no difference in symptoms was seen between the groups at 3 months follow-up although a reduced area of sensory loss was measured on the arm. To determine if longer follow-up provides evidence for ICBN preservation, follow-up of patients in the trial at 3 years (range 32-38 months) postoperatively was performed. METHODS: Sensory symptoms and deficits, pain, shoulder movements, arm circumference and the presence of neuromas were documented in 73 patients from the original group of 120. RESULTS: No difference in survival or axillary recurrence was observed. The only symptom which differed between the two groups was a subjective assessment of 'different sensation' (P=0.006). No significant difference was observed in other sensory symptoms, pain, shoulder movement, arm circumference or presence of neuromas. A larger area of sensory deficit was measured in women with sacrificed nerves compared to preserved (P=0.009). CONCLUSION: Preservation of the intercostobrachial nerve does not affect patient survival. It improves patient sensory deficit significantly and modestly improves long-term symptoms.

Adult↗
PubMed2002

Increased soluble intercellular adhesion molecule-1, breast cancer and the acute phase response.

Abnormal levels of soluble intercellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP) and von Willebrand factor (vWf) are commonly found in breast and other cancers. However, the relationship between these molecules is unclear as raised sICAM-1 and vWf may simply reflect an acute phase response. We tested the hypothesis that raised sICAM-1 and vWf are related to the acute phase response by measuring both markers by enzyme-linked immunosorbent assay, and CRP by dry chemistry, in 40 women with breast cancer (cases) and 40 age-matched controls. All three markers were raised in the cases compared with the controls [sICAM-1 (mean +/- SD), 281 +/- 70 versus 230 +/- 40 ng/ml; vWf (mean +/- SD), 139 +/- 33 versus 106 +/- 16 IU/dl; CRP (median), 7 (interquartile range, 5-11) versus 5 (4-6) mg/dl; all P < 0.01]. However, sICAM-1 correlated strongly with CRP (r = 0.67, P < 0.001) in the cases but there was no significant relationship between vWf and CRP (r = -0.15, P = 0.351). There were no significant correlations in the controls. We conclude that raised sICAM-1 in breast cancer, like the acute phase response, reflects inflammation, and that raised vWf seems likely to be independent of the acute phase response.

Acute-Phase Reaction↗
PubMed2001

Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ.

BACKGROUND: Breast conserving surgery (BCS) is common practice for unifocal ductal carcinoma in situ (DCIS) less than 4 cm in size, but the extent of tumor free margin width around DCIS necessary to minimize recurrence is unclear. METHODS: Clinical and pathologic details were recorded from all patients with pure DCIS < 4 cm in size, treated with BCS between 1978 and 1997. Histologic margins were measured by using an ocular micrometer. Patients with clear margins (> 1 mm) were divided up into 3 groups for analysis based on margin of normal tissue excised: 1.1-5 mm, 5.1-10 mm, and 10.1-40 mm. RESULTS: There were 66 patients with close margins (< or = 1 mm), of which 25 cases (37.9%) recurred. The recurrence rates for the 3 clear margin groups ranged from 4.5-7.1%. Median followup was 47 months (range 12-197 mos). Risk of recurrence in the group with close margins was greater than the subgroups with clear margins (P < 0.001); no differences in recurrence was seen between the individual subgroups with clear margins. Nuclear Grade 3 was predictive of recurrence (P = 0.03). Following excision alone, the recurrence rate was 18.6%, compared with 11.1% when radiotherapy was given as adjuvant therapy. Women with clear margins following excision had a recurrence rate of only 8.1%. CONCLUSION: After BCS for DCIS, close margins were associated with a high risk of local recurrence. Radiotherapy did not compensate for inadequate surgical clearance.

Adult↗
PubMed2001

Mixed apocrine/endocrine ductal carcinoma in situ of the breast coexistent with lobular carcinoma in situ.

An unusual mixed form of ductal carcinoma in situ (DCIS) of the breast is described, which exhibits a biphenotypic morphology encompassing a range of differential diagnostic DCIS subtypes. In addition, immunophenotypic and ultrastructural studies demonstrate neuroendocrine and apocrine differentiation, raising questions regarding appropriate classification and biological behaviour. In two cases, coexistence of this mixed form of DCIS with lobular carcinoma in situ (LCIS) in the same duct lobular units is an additional unusual feature that might, at least in some cases, indicate a closer relation between them.

Apocrine Glands↗
PubMed1999

Acute inflammatory (non-purulent) arthritis concomitant with a developing breast abscess.

A 34 year old female presented 7 weeks post-partum with acute diffuse arthritic manifestations and pyrexia. Extensive investigations (grossly raised erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], normal serology and others) were performed to pursue a diagnosis. Subsequently a breast abscess was diagnosed. Surgical treatment of this led to almost immediate resolution of the joint complaints and return of ESR/CRP to normal levels. This was considered a hitherto unreported case of acute non-purulent inflammatory arthritis concomitant to an existing infection elsewhere in the body. The pathogenic mechanism is unclear but speculatively toxin-mediated.

Abscess↗
PubMed1998

The importance of complete excision in the prevention of local recurrence of ductal carcinoma in situ.

Mastectomy probably represents over-treatment for the majority of women with screen detected ductal carcinoma in situ (DCIS) and breast-conserving surgery is now widely advocated. In this study, biopsy cavity shavings were used to ensure complete excision in 129 women undergoing breast-conserving surgery for screen detected DCIS. A margin was considered clear if DCIS was > 1 mm from any margin of excision and shavings were clear. Patients with involved margins (DCIS at resection margin) underwent re-excision, irrespective of shaving status. After re-excision, 101 women (78%) had clear margins and 28 (22%) close margins (DCIS < or = 1 mm from resection margin). Cavity shavings were histologically clear of DCIS in all cases. Ipsilateral DCIS recurrence occurred in 12 (9.3%) patients. Two recurrences also contained invasive carcinoma. The median time to diagnosis was 14 months and all recurrences occurred at the site of the previous biopsy. Seven recurrences were detected at the first annual mammogram, four at the second and one at the third. Ipsilateral recurrence was related to margin status; only 2 out of 101 (2%) patients with clear margins recurred, compared with 10 out of 28 (36%) patients with close margins. Local recurrence and close margin status both correlated with a high modified Van Nuys prognostic index score. Our results indicate that local relapse represents residual DCIS rather than true recurrence in the majority of cases. Cavity shavings have proved ineffective in ensuring complete excision. We now ensure a minimum 10 mm margin of excision around all screen-detected DCIS lesions.

Adult↗
PubMed1998

Prospective randomized controlled trial of preservation of the intercostobrachial nerve during axillary node clearance for breast cancer.

BACKGROUND: Complications of axillary surgery occur due to severance of the intercostobrachial nerve (ICBN). The feasibility and benefit of preserving the ICBN to prevent sensory loss was studied prospectively. METHODS: Sensory symptoms and deficits were documented, and shoulder movement and arm circumference were measured at discharge and 3 months later in 120 patients randomized to either preservation or division of the ICBN. RESULT: Preserving the ICBN was feasible in 39 (65 per cent) of the 60 patients randomized to the preservation group. Preserving the nerve prolonged the procedure by a median of 5 min. No difference in sensory symptoms between the groups was seen at 3 months. At 3 months 53 per cent of patients randomized to ICBN preservation had a sensory deficit compared with 84 per cent of those randomized to ICBN sacrifice (P < or = 0.05). CONCLUSION: Preserving the ICBN reduces the incidence of sensory deficit (but not symptoms) in patients after axillary clearance.

Adult↗
PubMed1997

Assessment of hormone dependence of comedo ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) represents 20%-30% of breast cancers detected by clinical screening (i.e., mammography). More than 50% of DCIS lesions may be estrogen receptor negative and, therefore, hormone independent. However, the role of estrogen in the natural history of DCIS is unknown. PURPOSE: A novel in vivo (i.e., xenograft) model was developed to determine to what degree DCIS lesions depend on estrogen for growth. METHODS: Specimens of breast tissue were collected from 52 women during diagnostic or therapeutic surgical procedures. Portions of each specimen were randomly selected and analyzed by histology and thymidine labeling (to measure cell proliferation). The remainder of each specimen was implanted into five to 18 athymic BALB/c nu/nu mice (depending on the amount of tissue available), with eight pieces of approximately 2 mm x 2 mm x 1 mm implanted at different locations on the back of each mouse. Half of the mice received implants containing estrogen (2 mg 17 beta-estradiol), and the other half received placebo implants. Levels of cell proliferation in xenografts, recovered after 14, 28, 42, or 56 days in the mice, were measured by thymidine labeling or by immunohistochemistry through use of an antibody specific for the Ki-67 nuclear antigen. Immunohistochemistry was also used to measure the levels of estrogen receptor in the tissue specimens. Serum 17 beta-estradiol levels in the mice were measured by radioimmunoassay. RESULTS: Initial levels of cell proliferation were approximately 10-fold higher in 10 specimens with estrogen receptor-negative, comedo (i.e., more malignant in appearance) DCIS than in four specimens with estrogen receptor-positive DCIS (mean proliferation indices: 22% versus 1.9%, respectively; two-sided P < .001). Xenografts from the majority of specimens survived up to 56 days in the mice and maintained good architectural and cellular preservation. Estrogen treatment of the xenograft-bearing mice had no effect on the high level of cell proliferation observed in estrogen receptor-negative, comedo DCIS specimens (two-sided P = .89). In contrast, increased levels of cell proliferation in response to estrogen supplementation were measured in three estrogen receptor-positive, noncomedo DCIS specimens (two-sided P < .001). However, even with estrogen treatment, cell proliferation levels in estrogen receptor-positive DCIS specimens did not reach those seen in estrogen receptor-negative DCIS specimens. CONCLUSION AND IMPLICATION: Estrogen receptor-negative, comedo DCIS lesions appear to be estrogen independent; therefore, antiestrogen (e.g., tamoxifen) therapy may not benefit patients with comedo DCIS.

Adult↗
PubMed1996

Cyclosporin A and multiple fibroadenomas of the breast.

Multiple bilateral fibroadenomas are uncommon. This finding in four women who had received renal transplants prompted further inquiry. A prospective study was performed on 39 women under the age of 55 years who had received a renal transplant at least 1 year earlier. Clinical examination and breast ultrasonography were performed. Factors considered included immunosuppressive therapy, concurrent medication and renal function. Blood was taken for estimation of oestradiol, prolactin, follicle-stimulating hormone (FSH) and sex hormone binding globulin levels. Fibroadenomas were found in 13 of 29 women who had received cyclosporin A: multiple in ten and bilateral in five. No abnormal breast findings were seen in 10 patients immunosuppressed with steroids and azathioprine alone (chi 2 = 7.30, 1 d.f., P < 0.01). Serum oestradiol concentration was raised in women with fibroadenomas compared with that in those with normal breasts (P < 0.05) and the level of FSH was lower (P < 0.01). Cyclosporin A may act on breast fibroblasts by humoral mechanisms and direct action.

Adult↗
PubMed1996

A comparison of axillary node status between cancers detected at the prevalence and first incidence breast screening rounds.

Screen-detected breast cancers are smaller than those detected in symptomatic populations and, for any given size, they are associated with fewer lymph node metastases. The management of axillary lymph nodes in patients with screen-detected breast cancer remains controversial. We have previously reported that prevalence (initial screen)-detected cancers are associated with nodal metastases in 17.4% of cases overall. Cancers < or = 10 mm, of any grade, are associated with metastases in only 5% of cases, and grade I cancers <30 mm are not associated with metastases. This led to our recommendation that axillary surgery is unnecessary for these groups of women. The present study compared the nodal status of cancers detected at the prevalence and first incidence (second) screens in order to determine whether our recommendation is appropriate for cancers detected at the first incidence screen. Overall, 30.1% of cancers detected in the first incidence screen presented axillary nodal metastases. At all size ranges, cancers detected at the first incidence screen were associated with significantly more lymph node metastases than prevalence-detected cancers. In particular, cancers < or = 10 mm were associated with metastases in 14.3% of cases. With the possible exception of grade I cancers, we believe that surgical staging of the axilla is essential for cancers detected at the first incidence screen, irrespective of size.

Aged↗
PubMed1996

Membranous fat necrosis of the breast.

To investigate the pattern and prevalence of membranous fat necrosis of the breast we examined 25 breast biopsies or mastectomy specimens performed for recurrent lumps following conservative surgery and radiation therapy. In addition, we examined 41 consecutive cases taken from our files coded as fat necrosis which were associated with several aetiologies. Our results demonstrate that membranous fat necrosis of the breast occurs in association with several aetiologies but in its florid form is most often due to radiation therapy.

Adipocytes↗
PubMed1995

Lobular carcinoma of the breast can be managed by breast-conserving therapy.

There has been a reluctance to treat patients with invasive lobular carcinoma by breast-conserving therapy because of the possibility of increased rates of local recurrence. This study is a retrospective review of 226 patients with pure invasive lobular carcinoma 4 cm or less treated by breast conservation therapy or mastectomy. Local relapse occurred in four of 52 patients (8 per cent) after breast conservation compared with 21 of 174 (12 per cent) after mastectomy. Breast conservation for invasive lobular carcinoma did not result in a higher incidence of local relapse and patients with invasive lobular and ductal carcinomas may be managed in a similar fashion.

Adult↗