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Age as a prognostic factor for breast and regional nodal recurrence following breast conserving surgery and irradiation in stage I and II breast cancer.

PURPOSE: To evaluate the association between age and breast/regional nodal relapse following breast conserving surgery and irradiation. METHODS AND MATERIALS: The results of treatment in 511 patients with 519 Stage I and II breast cancers treated at Mallinkrodt Institute of Radiology and affiliated hospitals between 1958 and 1988 were reviewed. RESULTS: Seventy women, of whom 96% had axillary dissections, were 39 years of age or younger. These young patients were more likely to have chemotherapy (p < 0.0001), and tumor bed reexcision (p < 0.01), and less likely to have an undissected axilla (p < 0.01), or estrogen receptor positive tumor (p = 0.02) than the older women (> 40 years). Although breast recurrence tended to appear earlier in the younger patients (12% at 5 years for those < 40 years vs. 6% at 5 years for those older), by 7 years the breast failure rate for the two groups was the same (12%), p = 0.13. In the 37 women 35 years of age or younger, the actuarial rate of breast recurrence was 9% at 7 years. Compared to other series in the literature, in which cancers were grossly excised without regard to the microscopic margins of resection, and reexcision was not routinely performed, young women treated with breast conserving surgery and irradiation at our institution frequently underwent reexcision of the tumor bed (57%), and had negative pathologic margins of resection (75%). Regional nodal relapse was in general uncommon, and not seen with increased frequency in the youngest cohort. CONCLUSION: Our experience suggests that young age is not a contraindication to breast conserving surgery and irradiation. Although breast cancers in this cohort may have certain features rendering them prone to local failure, we believe this risk can be mitigated by appropriate patient selection and optimal surgical resection.

Adult↗

Objective analyses of mastalgia in breast clinics: is breast pain questionaire a useful tool in a busy breast clinic?

The aim of this study was to investigate the feasibility of use of breast pain questionnaire (BPQ), a short, focussed and robustly designed tool to assess severity of mastalgia and its impact on quality of life, in a busy breast clinic. Seventy-four consecutive women completed BPQ prior to their consultation with a Breast Surgeon. Based on the BPQ score, mastalgia was graded as mild (score 0-100) in 26%, moderate (score 101-200) in 59% and severe (score >200) in 15% of patients. In 93% of patients breast pain lasted for more than 5 days and visual analogue score (VAS) was more than 3.5 in 82% of patients. The breast pain was described as mild (12%) discomforting (55%), distressing (22%) excruciating (3%) or horrible (8%). All results are presented as median (interquartile ranges). Out of maximum possible 100, overall pain rating was 17(9-31), percent sensory component was 21(12-33) and percent affective component was 0(0-17). The percent VAS was 60(40-80), percent pain index was 40(40-60) and quality of life score (maximum possible 60) was 20(0-40). Of maximum possible score of 360, total breast pain was 137(99-180). In conclusion BPQ can be used routinely in a busy breast clinic as a quick, user-friendly and reliable tool to assess the degree and severity of breast pain in order to provide an organised approach to the management of mastalgia.

Adult↗

A cost comparison analysis of partial versus whole-breast irradiation after breast-conserving surgery for early-stage breast cancer.

PURPOSE: To assess, if and for whom, there are cost savings associated with alternate breast radiotherapy (RT) techniques when compared with the conventional external beam-based whole-breast RT with a boost (WBRT-B). METHODS AND MATERIALS: Treatment planning and delivery utilization data were modeled for eight different breast RT techniques: (1) WBRT-B: 60 Gy in 30 fractions; (2) WBRT: 50 Gy in 25 fractions; (3) WBRT-accelerated (AC): 42.5 Gy in 16 fractions; (4) WBRT-intensity-modulated RT (IMRT): 60 Gy in 30 fractions; (5) accelerated partial breast irradiation (APBI)-IC, MammoSite: 34 Gy in 10 twice-daily fractions; (6) APBI-IT, HDR interstitial: 34 Gy in 10 twice-daily fractions; (7) APBI three-dimensional conformal RT (3D-CRT): 38.5 Gy in 10 twice-daily fractions; or (8) APBI-IMRT: 38.5 Gy in 10 twice-daily fractions. Costs incurred by payer (i.e., direct medical costs; 2003 Medicare Fee Schedule) and patient (i.e., direct nonmedical costs; time and travel) were estimated. Total societal costs were then calculated for each treatment approach. RESULTS: Not all efforts to reduce overall treatment time result in total cost savings. The least expensive partial breast-based RT approaches were the external beam techniques (APBI-3D-CRT, APBI-IMRT). Any reduced cost to patients for the HDR brachytherapy-based APBI regimens were overshadowed by substantial increases in cost to payers, resulting in higher total societal costs; the cost of HDR treatment delivery was primarily responsible for the increased direct medical cost. For the whole breast-based RT approaches, treating without a boost (WBRT) or with WBRT-AC reduced total costs. Overall, WBRT-AC was the least costly of all the regimens, in terms of costs to society; APBI approaches, in general, were favored over whole-breast techniques when only considering costs to patients. CONCLUSIONS: Based on societal cost considerations, WBRT-AC appears to be the preferred approach. If one were to pursue a partial-breast RT regimen to minimize patient costs, it would be more advantageous from a societal perspective to pursue external beam-based approaches such as APBI-3D-CRT or APBI-IMRT in lieu of the brachytherapy-based regimens.

Breast Neoplasms↗

Lumpectomy and breast radiotherapy in breast cancer patients with a family history of breast cancer, ovarian cancer, or both.

This article presents an outcomes review of breast cancer patients identified from the cancer registries of four area hospitals. These patients had family histories of breast cancer, ovarian carcinoma, or both and were treated with conservative surgery and radiation to the involved breast. Patients were as follows: group 1, one first-degree relative ( n = 165, one synchronous bilateral breast cancer); group 2, > or =2 first-degree relatives ( n = 21); group 3, one second-degree relative ( n = 20); and group 4, > or =2 second-degree relatives ( n = 18). The total of patients and breast cancer events was 224 and 225, respectively. Group 5 was a subgroup of 53 patients with a substantial risk (>10%) of a BRCA1 or BRCA2 mutation. After a median follow-up of 3.9 years, 5 patients had local failure (2%), and 5 developed a contralateral breast cancer (2%). There were no significant differences in local failure rates between groups (p = 1.0): group 1, 5 of 166 (3%); group 2, 0 of 21 (0%); group 3, 0 of 20 (0%); and group 4, 0 of 18 (0%). Local failure for group 5 was 2% (1 of 53). Four of 143 patients (3%) with a minimum 3 years of follow-up (median, 5.6 years) had local failure, and 5 (4%) developed a contralateral breast cancer. A univariate analysis was statistically significant for differentiation only (well, 0 of 67; moderately, 1 of 57 [1.8%]; poor, 3 of 26 [11.5%], p = 0.008). Overall survival for groups 1-4 did not differ significantly. Although follow-up has been relatively short, we have not found that breast cancer patients with various degrees of family histories of breast/ovarian carcinoma have had a detrimental outcome when treated with conservative therapy.

Analysis of Variance↗

Molecular specialization of breast vasculature: a breast-homing phage-displayed peptide binds to aminopeptidase P in breast vasculature.

In vivo phage display identifies peptides that selectively home to the vasculature of individual organs, tissues, and tumors. Here we report the identification of a cyclic nonapeptide, CPGPEGAGC, which homes to normal breast tissue with a 100-fold selectivity over nontargeted phage. The homing of the phage is inhibited by its cognate synthetic peptide. Phage localization in tissue sections showed that the breast-homing phage binds to the blood vessels in the breast, but not in other tissues. The phage also bound to the vasculature of hyperplastic and malignant lesions in transgenic breast cancer mice. Expression cloning with a phage-displayed cDNA library yielded a phage that specifically bound to the breast-homing peptide. The cDNA insert was homologous to a fragment of aminopeptidase P. The homing peptide bound aminopeptidase P from malignant breast tissue in affinity chromatography. Antibodies against aminopeptidase P inhibited the in vitro binding of the phage-displayed cDNA to the peptide and the in vivo homing of phage carrying the peptide. These results indicate that aminopeptidase P is the receptor for the breast-homing peptide. This peptide may be useful in designing drugs for the prevention and treatment of breast cancer.

Amino Acid Sequence↗

External breast prosthesis use: experiences and views of women with breast cancer, breast care nurses, and prosthesis fitters.

After mastectomy, the provision of an appropriate breast prosthesis can help to improve body image and quality of life and reduce associated emotional distress. Although up to 90% of women use an external breast prosthesis after mastectomy, little is known about their experiences and satisfaction with breast prosthesis use. Focus groups were conducted with women who had been fitted with an external breast prosthesis, breast care nurses, and prosthesis fitters to explore women's experiences of prosthesis use. Qualitative thematic content analysis of focus group transcripts indicated that whereas women's initial reaction to the prosthesis generally was negative, this improved over time. Provision of adequate information and support, characteristics of the fitter and the fitting experience, and relationships with breast care nurses and prosthesis fitters were important to women's acceptance and satisfaction with their prosthesis. The study results highlighted the key role that breast care nurses play and the underestimation of the prosthesis fitter's role. Common themes concerning the impact of prosthesis use included body image, appearance, and feminine identity. These findings have important implications for professionals involved in the delivery of breast prostheses services.

Adaptation, Psychological↗

Breast conservation treatment for patients presenting with axillary lymphadenopathy from presumed primary breast cancer: the role of breast magnetic resonance imaging for staging.

Three female patients presented with malignant axillary lymphadenopathy presumed to be from primary breast cancer. No evidence of primary cancer was found in the breast on either mammography or breast magnetic resonance imaging (MRI). All 3 patients underwent axillary lymph node dissection and systemic chemotherapy followed by radiation therapy to the breast and regional lymph nodes. Two patients remain relapse free with a follow-up of 3.7 years each. The third patient achieved locoregional control in the ipsilateral breast and regional lymph nodes but relapsed in the contralateral axilla. These 3 cases illustrate the potential for breast conservation treatment for patients presenting with axillary adenopathy from a presumed primary breast cancer but without either mammographic or breast MRI findings.

Axilla↗

Changing indications for breast conserving therapy: proportion of patients with operable breast cancer suitable for breast conservation.

The changes in indication for breast conserving therapy and the proportion of operable stage-I and stage-II breast cancers suitable for breast conserving therapy were studied in three time periods. The percentage of patients treated with breast conserving therapy gradually increased through the years: 77/199 (39%) in 1980-1981, 122/245 (50%) in 1985-1987, and 168/305 (55%) in 1987-1989. Using the actual selection criteria more patients might have been candidates for breast conserving therapy: 69, 64 and 59 per cent respectively. In the period 1987-1989 almost all patients who were considered good candidates for breast conserving therapy had a breast sparing procedure. Indications widened in relation to age limit (less than or equal to 70 years) and, over the years, more factors became relative contra-indications: very young age, presence of extensive intra-ductal component, data from mammography (multicentricity, size and aspect of the lesion). About 40 per cent of the patients were no appropriate candidates for breast conserving therapy. This percentage would be higher when operable stage-III patients would have been included.

Age Factors↗

Hematomas following excisional breast biopsies for invasive breast carcinoma: the influence of deep suture approximation of breast parenchyma.

The controversy over whether breast parenchyma should be approximated by suture after excisional biopsy is largely unresolved. The major debate is whether suture closure will decrease the incidence of hematomas and perhaps adversely alter the contour of the breast. To focus on the first question, we analyzed 162 patients undergoing mastectomy for breast cancer at Henry Ford Hospital between July 1988 and August 1992. All patients had previous excisional biopsies of breast lumps for diagnostic purposes. The cases were divided into two major groups depending on the placement or lack thereof of deep sutures in breast parenchyma. Of the total number of patients, 105 had deep suture approximation of breast parenchyma, whereas 57 did not. The biopsies were performed by 17 surgeons, although 72 per cent were done by four surgeons. Most of the surgeons varied their technique sporadically, but the number of cases most handled individually were too small for statistical analysis. Macroscopic and microscopic evaluation of the mastectomy specimen by the pathologist was used for definitive diagnosis of hematoma. The majority of these hematomas were of no clinical consequence and were usually not noted by the clinician. None of the hematomas required surgical drainage. Hematomas were determined pathologically in 64/162 patients (39.5%). Hematomas developed in 33/105 patients (31.4%) with deep wound approximation of breast parenchyma by suture compared to the higher rate seen in 31/57 patients (54.4%) without deep wound approximation (P = 0.004). This study supports the use of deep suture approximation after excisional biopsy for breast cancer.

Biopsy↗

The palpable breast lump: information and recommendations to assist decision-making when a breast lump is detected. The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Canadian Association of Radiation Oncologists.

OBJECTIVE: To provide information and recommendations for assisting women and their physicians in making the decisions necessary to establish or exclude the presence of cancer when a lump is felt in the breast. EVIDENCE: Guidelines are based on a systematic review of published evidence and expert opinion. References were identified through a computerized citation search using MED-LINE (from 1966) and CANCERLIT (from 1985) to January 1996. Nonsystematic review of breast cancer literature continued to January 1997. BENEFITS: Exclusion or confirmation of the presence of cancer with the minimum of intervention and delay. RECOMMENDATIONS: Investigation of women with a breast lump or suspicious change in breast texture starts with a history, physical examination and usually mammography. The clinical history should establish how long the lump has been noted, whether any change has been observed and whether there is a history of biopsy or breast cancer. Risk factors for breast cancer should be noted, but their presence or absence should not influence the decision to investigate a lump further. The physical examination of the breast should aim to identify those features that distinguish malignant from benign lumps. Mammography can often clarify the nature of the lump and detect clinically occult lesions in either breast. Fine-needle aspiration can establish whether the lump is solid or cystic. When a tumour is solid, cells can be obtained for cytologic examination. Ultrasonography is an alternative method to fine-needle aspiration for distinguishing a cyst from a solid tumour. Whenever reasonable doubt remains as to whether a lump is benign or malignant, a biopsy should be carried out. When surgical biopsy is used, the aim is to remove the whole lump in one piece along with a surrounding cuff of normal tissue. Core biopsy, either clinically or image-guided, can usually establish or exclude malignancy, thus reducing the need for surgical biopsy. Thermography and light scanning are not recommended diagnostic procedures. The value of magnetic resonance imaging is still under investigation. It is not a routine diagnostic procedure at this time. The choice of procedure should take into account the experience of the diagnostician and availability of the technology in question. The work-up should be completed expeditiously and the patient kept fully informed throughout. Even when malignancy is not found, it may be prudent, in some cases, to arrange follow-up surveillance. VALIDATION: Guidelines were reviewed and revised by the Writing Committee, expert primary reviewers, secondary reviewers selected from all regions of Canada and by the Steering Committee. The final document reflects a consensus of all these contributors.

Adult↗

In vivo 1H MRS of normal breast and breast tumors using a dedicated double breast coil.

Image-guided localized proton MR spectroscopy (MRS) of normal breasts and breast tumors (ductal and undifferentiated carcinomas) was performed using a dedicated double breast coil. In vivo 1H MR spectra from 10 normal volunteers showed signals from water and lipids only, even in breasts with small contribution of fatty breast tissue. In the spectra from 6 of the 12 examined patients, an intense signal assigned to choline compounds was detected. The signal was also detected at lower levels in the remaining patients. This study shows that in vivo 1H MRI/MRS examinations of breast tumors can be performed within an examination time of 45 to 60 minutes. Signals from breast tumor metabolites may be detected using in vivo 1H MRS.

Adult↗

Self examination of the breast: is it beneficial? Meta-analysis of studies investigating breast self examination and extent of disease in patients with breast cancer.

The question whether the aggregated published research suggests that breast self examination is beneficial was explored in a meta-analysis of 12 studies including a total of 8118 patients with breast cancer that related the practice of breast self examination to regional lymph node state or tumour diameter. Based on the six studies for which data were available, 39% of patients (1115/2852) who reported having done breast self examination at least once before their illness had evidence of cancer in the lymph nodes compared with 50% of women (1348/2713) who had not done the examination. Logistic regression analysis showed this difference to be significant (odds ratio 0.66, confidence interval 0.59 to 0.74). Combining six studies which reported the circumstances of detection disclosed that 42% of women (272/652) who found their tumour while doing breast self examination had evidence of cancer in the nodes compared with 46% of women (871/1901) who found the tumour accidentally; this difference was not significant. Analysis of eight studies which used the diameter of the tumour to indicate the extent of disease tended to confirm the findings on lymph node state, in particular the benefit of premorbid breast self examination. Significantly fewer women who had practised the examination before the illness (56%; 1205/2137) had tumours of 2 cm or more diameter compared with women who had not practised the examination (66%; 1500/2260). The combined odds ratio for that analysis was 0.56, confidence interval 0.38 to 0.81. These findings appear to be good evidence of the benefit of encouraging women to practise self examination of the breasts regularly.

Breast↗

Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Breast Cancer Linkage Consortium.

BACKGROUND: A few breast cancer cases are attributable to a hereditary predisposition to the disease. We aimed to compare the histological features of breast cancer in women carrying mutations in the susceptibility genes BRCA1 and BRCA2 with controls unselected for family history. METHODS: The morphological characteristics of specimens from 440 patients with familial breast cancer, including 118 in carriers of BRCA1 mutations and 78 in carriers of BRCA2 mutations, were compared with those from 547 age-matched controls, unselected for family history, by seven pathologists. FINDINGS: Cancers in carriers of BRCA1 (p < 0.0001) and BRCA2 mutations (p = 0.04) were, on average, of a higher overall grade than in controls. For example, the proportions in grade 3 were 66% of 139, 41% of 58 and 36% of 368 specimens, respectively. However, when the three grade indices were considered independently, breast cancers in BRCA1-mutation carriers showed more pleomorphism (p = 0.006), a higher mitotic count (p < 0.0001), and less tubule formation than controls (p = 0.006), whereas cancers in BRCA2-mutation carriers showed less tubule formation (p = 0.003), but no difference in pleomorphism or mitotic count. The occurrence of invasive lobular carcinoma and invasive ductal carcinoma was not significantly different between carriers of BRCA1 or BRCA2 mutations and controls. Medullary or atypical medullary carcinoma was, however, found more often in BRCA1 (13%, p < 0.0001) than in BRCA2-mutation carriers (3%) or controls (2%). Tubular carcinoma was less common in BRCA2-mutation carriers. The few mucoid carcinomas were all in familial cases. Carriers of BRCA1 mutations showed less ductal carcinoma in situ around the invasive lesion than controls (41 vs 56%, p = 0.001). Lobular carcinoma in situ was less common in familial cancers (p = 0.013), but differences were not significant for BRCA1-mutations or BRCA2-mutation carriers, separately. INTERPRETATION: The histology of breast cancers in predisposed women differs from that in sporadic cases, and there are differences between breast cancers in carriers of BRCA1 and BRCA2 mutations. The findings suggest that breast cancer due to BRCA1, has a different natural history to BRCA2 or apparently sporadic disease, which may have implications for screening and management.

Adenocarcinoma↗

Plasma concentration and activity of matrix metalloproteinase 2 and 9 in patients with breast disease, breast cancer and at risk of developing breast cancer.

Matrix metalloproteinases (MMPs) are involved in extracellular matrix modification and associated with invasive and metastatic behavior of human malignant tumors. Specifically, MMP2 and MMP9 are implicated in both early and late processes of tumor development. It is reported that MMPs occur as inactive precursors, active enzymes or enzyme inhibitor complexes in biological samples. However, there is limited knowledge on the role of each form in disease and/or the significance of changes in the plasma concentration and/or activity in breast cancer patients. The aim of this study was to determine if patients with breast cancer, benign disease and at risk for developing breast cancer display characteristic levels of active and/or total MMP2 and MMP9 in plasma. Concentration and activity of MMP2 and MMP9 were determined quantitatively in the plasma of 124 female volunteers diagnosed with breast cancer (n=31), benign disease (n=38), or determined by the Gail Model to be at high risk (n=31) or low risk (controls, n=24) of developing breast cancer. Data obtained was statistically analyzed to search for differences/patterns characteristic of each category. Concentration of total MMP2 was significantly lower in control individuals than benign, high risk (P<0.001 respectively) and breast cancer patients (P=0.002). Activity of total MMP2 was significantly lower in controls compared to cancer, benign and high risk patients (P<0.001 respectively). Attempts to build a predictive/descriptive model using canonical discriminant analysis (utilizing all eight features; concentrations and activity levels of active/total MMP2 and MMP9) enabled the distinction of the controls from the high risk, benign and cancer groups. Our results suggest that preoperative plasma concentration and activity of MMP2 and MMP9 may permit sub-classification of female patients with breast disorders.

Adult↗

Ongoing clinical experience utilizing 3D conformal external beam radiotherapy to deliver partial-breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We present our ongoing clinical experience utilizing 3D conformal radiation therapy (3D-CRT) to deliver partial-breast irradiation (PBI) in patients with early-stage breast cancer treated with breast-conserving therapy. MATERIALS AND METHODS: Thirty-one patients referred for postoperative radiation therapy after lumpectomy were treated with PBI using our previously reported 3D-CRT technique. Ninety-four percent of patients had surgical clips outlining the lumpectomy cavity (mean: 6 clips). The clinical target volume (CTV) consisted of the lumpectomy cavity plus a 10-mm margin in 9 patients and 15-mm margin in 22 (median: 15 mm). The planning target volume consisted of the CTV plus a 10-mm margin for breathing motion and treatment setup uncertainties. The prescribed dose (PD) was 34 or 38.5 Gy (6 patients and 25 patients, respectively) in 10 fractions b.i.d. separated by 6 h and delivered in 5 consecutive days. Patients were treated in the supine position with 3-5 beams (mean: 4) designed to irradiate the CTV with <10% inhomogeneity and a comparable or lower dose to the heart, lung, and contralateral breast compared with standard whole-breast tangents. The median follow-up duration is 10 months (range: 1-30 months). Four patients have been followed >2 years, 6 >1.5 years, and 5 >1 year. The remaining 16 patients have been followed <12 months. RESULTS: No skin changes greater than Grade 1 erythema were noted during treatment. At the initial 4-8-week follow-up visit, 19 patients (61%) experienced Grade 1 toxicity and 3 patients (10%) Grade 2 toxicity. No Grade 3 toxicities were observed. The remaining 9 patients (29%) had no observable radiation effects. Cosmetic results were rated as good/excellent in all evaluable patients at 6 months (n = 3), 12 months (n = 5), 18 months (n = 6), and in the 4 evaluable patients at >2 years after treatment. The mean coverage of the CTV by the 100% isodose line (IDL) was 98% (range: 54-100%, median: 100%) and by the 95% IDL, 100% (range: 99-100%). The mean coverage of the planning target volume by the 95% IDL was 100% (range: 97-100%). The mean percentage of the breast receiving 100% of the PD was 23% (range: 14-39%). The mean percentage of the breast receiving 50% of the PD was 47% (range: 34-60%). CONCLUSIONS: Utilizing 3D-CRT to deliver PBI is technically feasible, and acute toxicity to date has been minimal. Additional follow-up will be needed to assess the long-term effects of these larger fraction sizes on normal-tissue sequelae and the impact of this fractionation schedule on treatment efficacy.

Aged↗

Normal breast lobular architecture in breast biopsy samples from breast cancer cases and benign disease controls.

Rodent studies suggest a relationship between lobular maturation and breast cancer risk. Human data are sparse, and were developed using whole mounts of mastectomy or mammoplasty samples, without consideration of menstrual phase in premenopausal women. We studied normal breast lobules in relation to cancer risk in 284 women, using surgical biopsy material (mean two sections and 43.2 lobular structures per subject): 167 were premenopausal; 89 with breast cancer (cases) and 78 undergoing benign breast biopsy (controls). Of 117 postmenopausal women, 67 were cases and 50 were controls. Normal lobular type was classified based on size, and was designated predominant if it constituted 60% or more of the total lobules classified. The control group showed 66% type I, 34% type II and 1% type III lobules while cases showed 69% type I, 31% type II and 7% type III structures. Predominant lobule type showed no association with cancer (p = 0.9). Postmenopausal women had a substantially higher proportion of type I lobules compared to premenopausal women, irrespective of the parity or cancer status (p < 0.001). Lobule type was not associated with menstrual phase classified by dates; however, when menstrual phase was classified using breast morphological characteristics, type I lobules were more abundant in follicular phase and type II in the luteal phase (p < 0.001). In conclusion, we did not observe a relationship between lobular architecture and breast cancer susceptibility when using smaller breast samples usually available in epidemiological studies, but these data highlight the need for menstrual phase stratification in future investigations.

Adult↗

GalNAc glycoprotein expression by breast cell lines, primary breast cancer and normal breast epithelial membrane.

Over-expression of N-acetylgalactosamine glycoproteins as detected by binding of the lectin from Helix pomatia (HPA), is associated with metastatic competence and poor patient prognosis in a range of human adenocarcinomas. These glycoproteins remain poorly characterised, and their functional role has yet to be elucidated. This study describes characterisation of a range of human breast/breast cancer cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of interest, and their comparison with normal breast epithelium and a range of clinical breast carcinoma samples. Confocal and light microscopy studies revealed cytochemical HPA-binding patterns consistent with a fundamental disruption in normal glycobiosynthetic pathways attending increasing metastatic potential. We report the most complete comparative analysis of HPA-binding ligands from cultured breast cells, clinical breast carcinoma samples and normal breast epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein bands common to both clinical tumour samples and breast cell lines and 6 of these bands were also expressed by samples of normal breast epithelium, albeit at much lower levels. Moreover, very marked quantitative but not qualitative differences in levels of expression consistent with metastatic capability were noted.

Acetylgalactosamine↗

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗