Search PubMed⌕ Search

Biomedical subjects

C Holcombe

Publications and source records attributed to C Holcombe.

At least 19 recordsLinked to original sources
PubMed2004

Correlation of mRNA for oestrogen receptor beta splice variants ERbeta1, ERbeta2/ERbetacx and ERbeta5 with outcome in endocrine-treated breast cancer.

This study has been performed to test the hypothesis that different oestrogen receptor beta (ERbeta) splice variants may be important determinants of clinical parameters, including outcome, in post-menopausal women with breast cancer receiving adjuvant endocrine treatment but no chemotherapy. Splice variants ERbeta1, ERbeta2 and ERbeta5 have been analysed by semi-quantitative RT-PCR in a cohort of 105 patients with primary breast cancer. Clinical correlates included age, grade, size, nodal status, ERalpha, progesterone receptor, Ki67, relapse-free survival (RFS) and overall survival (OS). Seventy per cent of cases were ERbeta1 positive, 69% ERbeta2 positive and 70% ERbeta5 positive. Within the cohort, 47% were positive for all three variants while 10% were negative for all three. ERbeta1 exhibited no discernible relationship with disease outcome. ERbeta2 and ERbeta5 expression was significantly associated with better RFS (P<0.005), and ERbeta2 with better OS (P=0.0002). In multivariate analysis, ERbeta2 (P=0.006), nodal status and the level of Ki67 expression were independent predictors for RFS while ERbeta2 (P=0.0008) and Ki67 status were independent predictors for OS. In the ERalpha-positive cases, or in the subset of those receiving adjuvant tamoxifen, ERbeta2 was significantly associated with good RFS (P<0.0005) and was the only independent marker of OS. We conclude that precise identification of splice variants of ERbeta are more important assessors than is ERbeta1 alone of the biological status of individual breast cancers, and hence in predicting their response to endocrine therapy.

Alternative Splicing↗
PubMed2003

Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast.

The development of an invasive recurrence following treatment for ductal carcinoma in situ (DCIS) converts a non-fatal disease to one associated with mortality. To date, no pathological or molecular features have been found to predict for the type of recurrence. Previous studies have suggested that in DCIS angiogenesis may be an important factor in determining the transformation from in situ to invasive carcinoma. We looked at 355 cases of DCIS and found that 32 had subsequently developed recurrent disease. In these 32 cases and in matched controls, periductal vascular density was determined using morphometry and anti-endothelial antibodies, von Willebrand factor (vWF) and CD34. Vascular density was related to the risk of both invasive and in situ recurrence. Normal lobules at least 2 mm away were used as controls. Differences in the phenotype of individual blood vessels was detected by performing dual staining immunofluorescence on selected cases. The microvessel density (MVD), as detected with the CD34 antibody, was higher around foci of DCIS than around normal breast lobules (P=0.001). Furthermore, it was significantly higher in cases of DCIS that recurred (P<0.0001). The findings with the vWF antibody were less clear cut and suggested a trend in decreasing MVD with increasingly aggressive disease. Dual immunofluorescence staining shows that the increase in MVD seen around DCIS is due to an increase in CD34+/vWF-blood vessels. An increase in CD34+/vWF-of blood vessels may be able to predict cases of DCIS that are at a high risk of developing a recurrence.

Aged↗
PubMed2003

Thymidine phosphorylase expression and stromal vascularity in ductal carcinoma in situ of the breast.

AIMS: Periductal angiogenesis in ductal carcinoma in situ is associated with an increased risk of subsequently developing a recurrence. This study aimed to (1) identify the relation between periductal and stromal vascularity and recurrence and (2) determine whether thymidine phosphorylase (TP) is associated with angiogenesis or recurrence in ductal carcinoma in situ (DCIS). METHODS: Twenty cases of DCIS that did not subsequently recur, 20 that developed a subsequent in situ recurrence, and 12 that developed a subsequent invasive recurrence were investigated. Periductal and stromal (hotspot) microvessel density were determined quantitatively using antibodies to CD34 and von Willebrandt factor (vWF). TP expression by DCIS was assessed semiquantitatively using the H score method. RESULTS: Stromal and periductal microvessel density assessed by anti-vWF gave similar mean values, and showed a strong positive correlation. When angiogenesis was assessed with anti-CD34 this association was lost. Not only were the mean values for both types of microvessel density higher than those obtained with anti-vWF, but the periductal microvessel density was significantly greater than the stromal microvessel density. TP expression was associated with stromal microvessel density assessed with anti-vWF, but not with anti-CD34. TP expression was not related to recurrence. No significant difference was identified in TP expression or stromal vascularity in DCIS between cases that recurred as DCIS and those that recurred as invasive carcinoma. CONCLUSIONS: Recurrent in situ or invasive disease after excision of DCIS does not appear to be related to stromal microvessel density or to TP expression by DCIS cells.

Adult↗
PubMed2002

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast.

Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated with invasive carcinoma but no pathological or molecular features have yet been found to predict for the development of invasive disease. For a tumour to invade, it requires the formation of new blood vessels. Previous studies have described a vascular rim around ducts involved by ductal carcinoma in situ, raising the possibility that the characteristics of periductal vascularisation may be important in determining transformation from in situ to invasive disease. Periductal vascular density and phenotype were determined using morphometry and a panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and CD34) and related to the presence of invasive carcinoma and other histological features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a greater density of CD34+ and CD31+ vessels but a decrease in those that were immunopositive for vWF, indicating a difference in phenotype and in density. Ductal carcinoma in situ associated with invasive carcinoma showed a profile of vascular immunostaining similar to that of pure ductal carcinoma in situ but there were significantly greater numbers of CD34+ and CD141+ vessels and fewer staining for vWF. There was a significant negative correlation between vascular density and both the cross-sectional areas of the ducts involved and the extent of the necrosis of the tumour they contained. A correlation between vascular density and nuclear grade was also noted, being highest in the intermediate grade. The greater density of CD34+ and CD141+ vessels around ductal carcinoma in situ associated with invasive carcinoma could reflect a greater predisposition to invade but a direct effect of co-existent invasive carcinoma cannot entirely be ruled out in the present study. The relationship between vascular density, grade, duct size and nuclear grade suggests that periductal angiogenesis increases with tumour growth rate but is unable to keep pace with the most rapidly growing lesions.

Antigens, CD34↗
PubMed2001

Psychological characteristics of women presenting with breast pain.

OBJECTIVE: Extensive evidence links unexplained physical symptoms in adults with childhood abuse. This study investigated a possible link between unexplained breast pain, recalled childhood abuse and emotional and somatic distress. METHODS: Consecutive female out-patients presenting with breast pain were categorised as treatment-resistant (n=20), newly diagnosed and requesting treatment (n=37), or newly diagnosed but reassured and not seeking treatment (n=32) and compared with pain-free patients with breast lumps (n=31). RESULTS: All breast pain groups were more anxious and depressed, somatised more and recalled a higher incidence of emotional abuse by comparison with breast lump patients. Logistic regression confirmed that emotional abuse and anxiety were independently associated with breast pain. CONCLUSION: Clinical management of patients who present breast pain should be sensitive to the evidence that pain is a marker of emotional abuse in some women and is associated with widespread somatic and emotional distress.

Adolescent↗
PubMed2001

Effects of early discharge following breast surgery.

A small group of breast cancer surgery patients were discharged early with axillary drains in situ. The group was examined for wound infection, seroma formation and depression, and compared to a group who stayed in hospital. There was no indication that early discharge increased seroma formation or infection. Anxiety and depression appeared to be less in the early discharge group.

Anxiety↗
PubMed2000

Current patterns of referral in breast disease.

The aim was to audit symptomatic referrals to this breast unit in 1998, in order to ascertain the main diagnosis in relation to age, and thereby identify the percentage and age of patients who were reassured and discharged without investigation. 3199 general practitioner referrals were seen in 1998. Of these, 8.7% (n=274) were diagnosed as cancer and 91.3% (n=2925) were given a non-malignant diagnosis. In those under 40 years, only 18 patients of the 1231 seen were diagnosed with cancer, and only one of these was younger than 30 years (29 years). Twenty-seven per cent (n=333) of women under 40 were diagnosed as normal, and of these 14% (n=174) had no investigation. We confirm the recommendations of the guidelines issued by the Department of Health, that in younger women without discrete lumps or family history, clinical examination and reassurance is adequate. This audit should therefore empower general practitioners, to confidently reassure the younger patient, without a discrete lump.

Journal Article↗
PubMed1999

The differential diagnosis and management of breast lumps in the tropics.

Breast cancer is less common in the Tropics than in the West, but presents a formidable challenge due to late presentation. Public education is vital if the outcome is to be improved. There are many benign pathologies which present similarly to cancer--this underlines the need for proper diagnosis, as mastectomy is often not necessary. It is important to remember that non-peurperal breast abscesses may be the first sign of HIV infection.

Adult↗
PubMed1998

Complications of latissimus dorsi myocutaneous flap breast reconstruction.

AIMS: To review the experience of a single unit in post-mastectomy reconstruction using the latissimus dorsi flap. METHODS: A retrospective review of 111 cases treated between 1984 and 1993. The notes were evaluated for type of procedure, associated treatment and complications. RESULTS: A significant morbidity of this procedure was demonstrated with 41 (37%) patients requiring a second operation during the period of the study. The majority of these second operations were related to the prosthesis used to achieve symmetry. Second operations were more common in those who had saline-filled prostheses. Other complications seen included wound infection, small areas of flap necrosis, hypertrophic scars and problems with the donor scar. No differences in complication rates were demonstrated for delayed vs immediate procedures or for patients receiving or not receiving radiotherapy. No life-threatening complication were seen during the study. CONCLUSIONS: The latissimus dorsi reconstruction is reliable but the overall programme is beset with considerable morbidity. This factor needs to be taken into consideration when discussing reconstructive options with the post-mastectomy patient.

Adult↗
PubMed1997

Is a histological section representative of whole tumour vascularity in breast cancer?

The assessment of a tumour's angiogenic potential, by measuring the microvessel density in histological sections, assumes that a 4-microm section is representative of whole tumour vascularity. This study has examined this assumption by comparing the vessel density found radiologically, after injecting specimens with contrast, with that found immunohistochemically. Twenty-one breast angiograms were performed following mastectomy for carcinoma and graded 1-3 for vessel density. Sections (4 microm) from these carcinomas were labelled for endothelial cells using anti-CD34, and the vessel counts were compared with the radiological grades. A significant correlation was found between the densities (P < 0.003, Kruskal-Wallis one-way ANOVA). We therefore conclude that the microvessel density measured in histological sections is representative of whole tumour vascularity.

Adult↗
PubMed1995

Blood flow in breast cancer and fibroadenoma estimated by colour Doppler ultrasonography.

Blood flow was measured by colour Doppler ultrasonography in 33 fibroadenomas of size 5-31 mm and 28 malignant breast masses of 8-37 mm visible on ultrasonography. There was detectable blood flow in 11 fibroadenomas and 21 cancers (P < 0.01). The median peak systolic frequency was 1.0 (range 0.25-2.0) kHz in malignant tumours and 0.5 (range 0.2-1.25) kHz in fibroadenomas. Blood flow was not detected in the eight fibroadenomas of less than 13 mm but was present in five of seven cancers smaller than this. Five of six carcinomas with three or more detectable vessels were classified as grade III on histological examination, compared with two of 11 carcinomas with one or two vessels. Similarly, five of seven cancers with three or more detectable vessels had axillary lymph node metastases compared with two of 13 with only one or two vessels. Detectable blood flow in breast masses is more common in cancer than in fibroadenoma and is highly suggestive of malignancy if the mass is less than 13 mm in size. Malignant tumours with a larger number of vessels are more likely to be of high grade and to have associated axillary node metastases.

Adolescent↗
PubMed1995

The satisfaction and savings of early discharge with drain in situ following axillary lymphadenectomy in the treatment of breast cancer.

A pilot study was performed to determine if early discharge with the drain in situ following axillary lymphadenectomy is feasible and safe. One hundred and one women who had axillary lymphadenectomy as part of their breast cancer treatment were studied. Ninety-six were offered early discharge with the axillary drain in situ, five were unsuitable for early discharge. The cohort who opted for early discharge (n = 39) had a lower rate of seroma formation (18% vs 34%) and a reduction in median hospital stay of 5 days. Patient satisfaction was high in both groups and there were no complications associated with early discharge or drain displacement. Early discharge after axillary lymphadenectomy with the axillary drain in situ is safe, feasible, popular with patients and offers considerable resource savings.

Adult↗