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PubMed1994

Radiotherapy in the curative treatment of breast cancer: current status and future trends. An opinion sample of radiation oncologists active in breast cancer research.

A questionnaire regarding the current practice of breast cancer radiotherapy and possible future trends in this field was filled out by 13 radiation oncologists active in breast cancer research. In the opinion of this small group, radiotherapy is presently included in the initial treatment of the large majority of early breast cancers, particularly in the framework of breast-conserving therapy, which is currently used in > 50% of these patients. Indications for post-mastectomy irradiation vary greatly among respondents, as do attitudes toward the potentially negative aspects of adjuvant radiotherapy. Most respondents feel that their future practices will be significantly influenced by an increase in screen-detected cancers, the aging of the population, the increasing influence of medical oncologists, participation in clinical trials, and increased patient participation in treatment decisions. An increase is foreseen in the use of breast-conserving approaches, radiotherapy, and systemic therapies, and a decrease in the use of both total mastectomy and axillary dissection. Most respondents feel that there will be a modest decrease in the percentage of conservatively operated patients receiving radiotherapy. A future role is seen for neo-adjuvant chemotherapy, at least in well-defined subgroups, increasing the number of patients offered breast-conserving approaches. Most respondents expect that irradiation of lymph nodal areas will gain new credibility and be used more often. No majority opinion could be elicited regarding ways of improving the therapeutic ratio in breast cancer radiotherapy.

Aged↗
PubMed1995

Breast conservation treatment of early stage breast cancer: patterns of failure.

PURPOSE: This study retrospectively assesses the patterns of failure in conservatively treated early stage breast cancer patients by correlating various clinical, pathologic, and treated-related factors with local, axillary, and distant relapse. METHODS AND MATERIALS: Between 1973 and 1990, 796 patients (817 breasts) received breast conservation surgery followed by radiotherapy. Local recurrences were counted as events even if they occurred simultaneously or after the appearance of axillary or distant metastases. RESULTS: The 10-year actuarial relative disease-free survival (DFS) rate for T1N0, T2N0, and T1-2N1 was 82%, 71%, and 54%, respectively. Stage N0 patients had a significant DFS advantage over N1 patients (p = 0.02). The 15-year actuarial local recurrence-free rate for T1 and T2 tumors was 82% and 87%, respectively (p = nonsignificant). Univariate analysis identified three significant risk factors for local relapse: (a) 48 breasts with tumors showing an extensive intraductal component had a crude local recurrence rate of 23% compared to 8% for 769 breasts without intraductal component (p = 0.0016); (b) the actuarial 10-year local recurrence-free rate for patients under age 40 years was 64% compared to 88% for patients over 40 years (p < 0.0001); (c) the 10-year actuarial local recurrence-free rate for 416 postmenopausal women without adjuvant tamoxifen was 83% compared to 97% for 107 postmenopausal women with tamoxifen (p = 0.0479). Salvage therapy for operable local recurrent patients resulted in a 8-year actuarial DFS rate of 47%, significantly lower than that obtained with primary treatment. The incidence of axillary relapse as the first sign of recurrence was 2%, and could be correlated with the lack of axillary dissection (p < 0.0000005) and primary tumor size (p = 0.03). Radiotherapy to the axilla did not influence axillary relapse. Actuarial 5-year DFS rate after treatment of isolated axillary recurrence was 27%. Axillary failure was a marker for distant failure. Contralateral breast cancer occurred in 8% of patients and did not have a detrimental effect on survival. Adjuvant tamoxifen decreased the 9-year actuarial incidence of contralateral breast cancer from 10% to 4% (p = 0.053). CONCLUSIONS: Tumors with extensive intraductal component, age under 40 years, and the omission of adjuvant tamoxifen in postmenopausal women increased local recurrence rate. Stage T2 and the lack of axillary dissection increased axillary recurrence rate. Stage N+ and local or axillary relapse increased distant failure rate. Axillary irradiation did not influence locoregional control nor survival. Improved therapy is needed for relapsing patients.

Actuarial Analysis↗
PubMed1996

Psychosocial adjustment and quality of life in women with breast cancer and benign breast problems: a controlled comparison.

Comparison of psychosocial adjustment in women with breast cancer (BC) and women with benign breast problems (BBP) has been hampered by a failure to control for age differences between these groups, as well as a failure to assess positive psychosocial adaptation in addition to psychological distress. Age-matched women with breast cancer (n = 80) and benign breast problems (n = 80) completed measures of psychological distress, positive psychosocial adaptation, and general quality of life (QOL). Breast cancer patients had completed primary treatment for breast cancer a mean of 24.6 months prior to participation (range, 6-57 months). Comparison of the BC and BBP groups indicated that the BC group reported (1) poorer physical health and functioning, (2) no differences in psychological distress, and (3) greater positive psychosocial adaptation, such as improved life outlook, enhanced interpersonal relationships, and deeper spiritual and religious satisfaction. Results support the theoretical position that cancer is a transitional event, that is, a traumatic event that alters an individual's assumptive world with the potential to produce long-lasting changes of both a positive as well as negative nature. This underscores the importance of using measures of both psychological distress and positive psychosocial adaptation when assessing psychological adjustment following transitional events such as breast cancer.

Adaptation, Psychological↗
PubMed1994

Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk.

Patients bearing macrocysts of the breast are at higher risk of later developing cancer. The fluid filling the cysts (breast cysts fluid, BCF) contains unusual amounts of steroid conjugates, first androgen and estrogen sulfates. Measuring BCF cations (K+,Na+) allows categorization of cysts into two major subsets (type I and type II) that are associated with a different degree and/or turnover of apocrine metaplastic cells in the lining epithelium. Type I cysts (high K+/Na+ ratio) accumulate hugh amounts of dehydroepiandrosterone sulfate, estrone sulfate, androstane-3 alpha,17 beta-diol glucuronide, androsterone glucuronide and contain more testosterone and dihydrotestosterone than type II. Conversely, type II cysts (low K+/Na+ ratio) contain more progesterone and pregnenolone. A cohort study was started in 1983 at the Cancer Prevention Center, Ravenna, Italy, with the aim of evaluating the relationships between the biochemistry of BCF and the incidence of breast cancer in women with gross cystic disease (GCD) of the breast. The bimodal distribution of the cationic pattern has been confirmed from data obtained in 798 patients aspirated. The risk of cyst relapse was significantly higher among women with type I cysts or with multiple cysts at presentation. Twelve incident cases of breast cancer have been diagnosed among women whose BCF was categorized. Eleven out of 12 cases had type I or multiple cysts. The cumulative incidence of breast cancer among patients bearing type I cysts was 2.5%. We conclude that women with GCD bearing type I cysts have an increased breast cancer risk when compared with the counterpart bearing type II cysts or the general population.

Adult↗
PubMed2004

Breast-conserving therapy and sentinel lymph node biopsy are feasible in cancer patients with previous implant breast augmentation.

BACKGROUND: Breast-conserving therapy (BCT) is reported to result in a significant rate of complications and local recurrences in patients with prior implant breast augmentation. The role of sentinel lymph node (SLN) biopsy in these patients is unknown. METHODS: Retrospective review of patients with prior breast augmentation treated with BCT or SLN biopsy. RESULTS: Nineteen breast cancers were treated with BCT. Of 17 breasts undergoing adjuvant radiotherapy, 11 (64.7%) retained favorable aesthetic results. Of 9 subpectoral implants, capsular contracture developed in only 1 (11.1%). During follow-up (median 3 years), 1 local recurrence (5.3%) occurred in a patient who refused adjuvant radiotherapy and systemic therapy. Eleven patients underwent SLN biopsy with an identification rate of 100% and a false-negative rate of 0%. CONCLUSIONS: Breast-conserving therapy inclusive of radiotherapy after implant breast augmentation produced acceptable cosmetic results in nearly two-thirds of patients. Sentinel lymph node mapping in the setting of prior implant augmentation was highly successful and accurate.

Adult↗
PubMed2006

Delayed breast cellulitis: an evolving complication of breast conservation.

PURPOSE: Delayed breast cellulitis (DBC) is characterized by the late onset of breast erythema, edema, tenderness, and warmth. This retrospective study analyzes the risk factors and clinical course of DBC. METHODS AND MATERIALS: From 1985 through 2004, 580 sequential women with 601 stage T0-2N0-1 breast cancers underwent breast conserving therapy. Cases of DBC were identified according to accepted clinical criteria: diffuse breast erythema, edema, tenderness, and warmth occurring >3 months after definitive surgery and >3 weeks after radiotherapy. Potential risk factors analyzed included patient comorbidity, operative technique, acute complications, and details of adjunctive therapy. Response to treatment and long-term outcome were analyzed to characterize the natural course of this syndrome. RESULTS: Of the 601 cases, 16%, 52%, and 32% were Stage 0, I, and II, respectively. The overall incidence of DBC was 8% (50/601). Obesity, ecchymoses, T stage, the presence and aspiration of a breast hematoma/seroma, removal of >5 axillary lymph nodes, and arm lymphedema were significantly associated with DBC. The median time to onset of DBC from the date of definitive surgery was 226 days. Ninety-two percent of DBC patients were empirically treated with antibiotics. Fourteen percent required more invasive intervention. Twenty-two percent had recurrent episodes of DBC. Ultimately, 2 patients (4%) underwent mastectomy for intractable breast pain related to DBC. CONCLUSION: Although multifactorial, we believe DBC is primarily related to a bacterial infection in the setting of impaired lymphatic drainage and may appear months after completion of radiotherapy. Invasive testing before a trial of antibiotics is generally not recommended.

Adult↗
PubMed2005

Breast conservation after neoadjuvant chemotherapy for stage II carcinoma of the breast.

BACKGROUND: Neoadjuvant chemotherapy has become the standard treatment for stage III breast cancer. Gratifying results in these patients prompted this prospective, nonrandomized study of neoadjuvant chemotherapy in stage II breast cancer. This study presents our experience with neoadjuvant chemotherapy in 127 patients with stage II carcinoma of the breast. STUDY DESIGN: Patients with stages IIA (T > 3.0 cm) and IIB carcinoma were considered for this study and underwent treatment with cyclic chemotherapy until a plateau of response was achieved. Responders underwent breast conservation or mastectomy according to conventional assessment. Chemotherapy was continued in the adjuvant setting. Survival data were compared with historic controls. RESULTS: Between 1981 and 2001, 127 women between the ages of 22 and 80 years (mean age 52, median age 50), with stage II breast cancer were enrolled, with median followup of 60 months. One hundred twenty-two patients (96.1%) responded to chemotherapy. Of this group, 35 (29.2%) experienced complete pathologic responses or had only microscopic foci of disease after treatment. Sixty-two patients (52.5%) had negative lymph nodes at the time of the operation; 28 of these patients were previously considered N-1 clinically. Seventy-six patients (62%) underwent breast conservation. Overall survivals at 5 years for stage IIA and IIB disease were 94.7% and 88%, respectively. Disease-free survival at 5 years was 85.2% for stage IIA patients and 69.1% for stage IIB patients. CONCLUSIONS: Neoadjuvant chemotherapy can be effectively applied to patients with stage II disease, and breast conservation becomes feasible in the majority of patients. When compared with historic controls, the current study suggests a statistically significant overall survival advantage (p < 0.007) at 5 years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1976

Breast cancer and preceding clinical benign breast disorders. A chance association.

A review of 1059 patients seen in office consultation from 1970 to 1975 for breast disorders revealed that patients with clinically benign disorders were six times as numerous as those with breast cancer. Only 11% of patients with breast cancer had had a previous benign breast-biopsy specimen and on average they were 20 years older than the peak age for benign clinical disease. Of the 163 patients with a previous benign breast-biopsy specimen only 14 (9%) had breast cancer compared with 13% in women without such a history. It is concluded that clinical benign breast disorders do not predispose patients to cancer, and such women should not be singled out for special study.

Adenofibroma↗
PubMed2001

Long-term results of local recurrence after breast conservation treatment for invasive breast cancer.

PURPOSE: The outcome for women with a local failure after breast conservation treatment is not well described in the literature. Because local recurrence is a potentially salvageable event, this study was performed to evaluate the outcome of patients with local recurrence after breast conservation surgery and definitive radiation treatment. METHODS AND MATERIALS: The study population consisted of 112 patients with ipsilateral breast tumor recurrence. There were 100 isolated local recurrences and 12 local-plus-regional recurrences. There were 93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local recurrences. Local recurrences were detected by physical examination alone in 42 patients, mammography alone in 47 patients, and both modalities in 23 patients. All patients were initially treated with breast conservation treatment with or without systemic therapy and subsequently treated at the time of local recurrence with salvage mastectomy with or without systemic therapy. The mean and median follow-up times after local recurrence were 49 and 44 months, respectively. RESULTS: For the entire group of 112 patients, the overall survival at 10 years after local recurrence was 69%, the cause-specific survival was 71%, and the freedom from distant metastases was 47%. For the 93 patients with an invasive local recurrence, the overall survival at 10 years was 64%, cause-specific survival was 67%, and freedom from distant metastases was 44%. For the 93 patients with an invasive local recurrence, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) also predicted for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On multivariable analysis, interval from diagnosis to local recurrence was an independent predictor of overall survival (p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) was borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%, respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that predicted for freedom from distant metastases were identified. There were three second locoregional failures on the chest wall. Two of the 19 patients with a DCIS local recurrence have died of metastatic breast cancer. Death was probably not related to their local recurrence, but rather a result of persistent risk from an invasive primary cancer. CONCLUSIONS: This analysis provides long-term data after salvage treatment for patients who experience local recurrence after breast conservation treatment. The variables of method of detection and interval from diagnosis to local recurrence are identified as having prognostic significance for overall and cause-specific survival. In view of the potential for long-term survival, aggressive attempt at salvage treatment is warranted for the patient with local recurrence after breast conservation treatment. Second local recurrence after salvage mastectomy is an uncommon event. Although DCIS local recurrences may not in themselves cause an increase in the risk of mortality, the risk from the primary invasive cancer persists.

Adult↗
PubMed2002

Repeat high-dose external beam irradiation for in-breast tumor recurrence after previous lumpectomy and whole breast irradiation.

PURPOSE: To determine whether excision of an in-breast tumor recurrence (IBTR) plus 5000 cGy in 25 fractions to the new operative area is both tolerated and effective as treatment for an IBTR after previous lumpectomy and whole breast irradiation. METHODS AND MATERIALS: Thirty-nine women with an IBTR after lumpectomy and breast irradiation for invasive carcinoma (n = 31) or ductal carcinoma in situ (n = 8) were treated with excision of the IBTR and radiotherapy (RT), 5000 cGy in 25 fractions, to the operative area using electrons of appropriate energy. The interval from completion of the first course of RT to diagnosis of the IBTR ranged from 16 to 291 months (median 63). RESULTS: The repeat course of RT to the new operative area was well tolerated in all patients, and no late sequelae occurred other than skin pigmentation changes. Eight patients, including 2 with suspicious bone scans at the time of IBTR, developed distant metastases, and 7 died 21-71 months (median 48) after retreatment. One patient was alive with distant metastases at 27 months after retreatment. Four of the 8 patients who developed distant metastases also had a second IBTR, and 3 died with persistent disease in the breast. An additional 4 patients, for a total of 8, had a second IBTR. Three were alive and free of disease after mastectomy, and 1 was alive and free of disease after mastectomy and additional RT for chest wall recurrence. An additional patient developed recurrence in the axilla 9 months after reirradiation and was treated with surgery; she died free of disease at 63 months. One patient underwent mastectomy for suspected persistent disease 2 months after completion of repeat RT; no evidence of recurrent tumor was found in the removed breast. Thus, 30 women (76.9%) had an intact breast free of tumor at death or at last follow-up 1-180 months (median 51.5) after reirradiation. Using the Kaplan-Meier life table analysis, the estimated overall and disease-free 5-year survival rate for the 39 patients was 77.9% and 68.5%, respectively. CONCLUSION: For select patients with an IBTR after lumpectomy and breast irradiation, excision of the IBTR followed by repeat external beam RT to the operative area may be an acceptable alternative to mastectomy.

Adult↗
PubMed2003

Dose-volume analysis of radiotherapy for T1N0 invasive breast cancer treated by local excision and partial breast irradiation by low-dose-rate interstitial implant.

PURPOSE: To evaluate the toxicity of partial breast irradiation (RT) using escalating doses of low-dose-rate interstitial implant as the sole adjuvant local therapy for selected T1N0 breast cancer patients treated by wide local excision. The results of a European Organization for Research and Treatment of Cancer study have demonstrated a significant local control benefit using external beam RT to 65 Gy compared with 50 Gy. Thus, the tolerance of escalating doses of partial breast RT should be determined, because this approach may become a standard treatment for patients with early-stage breast cancer. METHODS AND MATERIALS: Between 1997 and 2001, 48 patients with T1N0M0 breast cancer were enrolled into an institutional review board-approved Phase I/II protocol using low-dose-rate brachytherapy implants after wide local excision and lymph node staging surgery. Brachytherapy was started 3-4 days after surgery at a dose rate of 50 cGy/h, using (192)Ir sources evenly spaced to cover 3 cm around the resection margins. Typically, 2-3 planes were used, with a median of 14 catheters (range 10-16). The total dose was escalated in three groups: 50 Gy (n = 19), 55 Gy (n = 16), and 60 Gy (n = 13). The implant volume was calculated and used to classify patients into quartiles: 76-127 cm(3) (n = 12), 128-164 cm(3) (n = 12), 165-204 cm(3) (n = 12), and >204 cm(3) (n = 12). Cosmesis, patient satisfaction, treatment-related complications, mammographic abnormalities, rebiopsies, and disease status were recorded at each scheduled patient visit. RESULTS: The median follow-up for all patients was 23.1 months (range 2-43). Very good to excellent cosmetic results were observed in 91.8% of patients. Ninety-two percent of patients were satisfied with their cosmetic outcome and said they would choose brachytherapy again over the standard course of external beam RT. Six perioperative complications occurred: two developed bleeding at the time of catheter removal, two had abscesses, one developed a hematoma, and one had a nonhealing sinus tract requiring surgical intervention. Significant fibrosis (moderate-to-severe scarring and thickening of the skin and breast) was noted in only 4 patients; 1 had received 55 Gy and 3 had received 60 Gy. Abnormal posttreatment mammograms were seen in 19 patients. Eight patients underwent rebiopsy for abnormalities found either by mammography or on physical examination; all proved to be fat necrosis or post-RT changes. The rebiopsy rates appeared to correlate with doses >/=55 Gy (6 [75%] of 8 compared with 29 [60%]of 48 overall) and implant volumes >/=128 cm(3) (7 [87.5%] of 8 compared with 36 [75%] of 48 overall). To date, no local, regional, or distant recurrences have been observed. CONCLUSION: Low-dose-rate implants up to 60 Gy were well-tolerated overall. With an implant dose of 60 Gy, the incidence of posttreatment fibrosis (25%) appeared to be increased. Only the long-term follow-up of this and other implant studies will allow an understanding of the total radiation dose necessary for tumor control and the volume of breast that requires treatment.

Adult↗
PubMed1999

Validation of the methods of cosmetic assessment after breast-conserving therapy in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer.

PURPOSE: To evaluate both qualitative and quantitative scoring methods for the cosmetic result after breast-conserving therapy (BCT), and to compare the usefulness and reliability of these methods. METHODS AND MATERIALS: In EORTC trial 22881/10882, stage I and II breast cancer patients were treated with tumorectomy and axillary dissection. A total of 5318 patients were randomized between no boost and a boost of 16 Gy following whole-breast irradiation of 50 Gy. The cosmetic result was assessed for 731 patients in two ways. A panel scored the qualitative appearance of the breast using photographs taken after surgery and 3 years later. Digitizer measurements of the displacement of the nipple were also made using these photographs in order to calculate the breast retraction assessment (BRA). The cosmetic results after 3-year follow-up were used to analyze the correlation between the panel evaluation and digitizer measurements. RESULTS: For the panel evaluation the intraobserver agreement for the global cosmetic score as measured by the simple Kappa statistic was 0.42, considered moderate agreement. The multiple Kappa statistic for interobserver agreement for the global cosmetic score was 0.28, considered fair agreement. The specific cosmetic items scored by the panel were all significantly related to the global cosmetic score; breast size and shape influenced the global score most. For the digitizer measurements, the standard deviation from the average value of 30.0 mm was 2.3 mm (7.7%) for the intraobserver variability and 2.6 mm (8.7%) for the interobserver variability. The two methods were significantly, though moderately, correlated; some items scored by the panel were only correlated to the digitizer measurements if the tumor was not located in the inferior quadrant of the breast. CONCLUSIONS: The intra- and interobserver variability of the digitizer evaluation of cosmesis was smaller than that of the panel evaluation. However, there are some treatment sequelae, such as disturbing scars and skin changes, that can not be evaluated by BRA measurements. Therefore, the methods of cosmetic evaluation used in a study must be chosen in a way that balances reliability and comprehensiveness.

Adult↗
PubMed2003

What is the impact of breast augmentation on the Breast Screening Programme?

AIMS: To identify the number of women with breast implants in the Newcastle Breast Screening Programme, it's additional workload and compare the number of screen detected cancers in the implant and non-implant group. METHODS: Retrospective 9 year review of all women with cosmetic breast augmentation who have joined the National Breast Screening Programme in Newcastle. RESULTS: The percentage of total screened attendances involving implants has increased from 61 (0.10%) in 1990-93 to 97 (0.14%) in 1993-96 and 135 (0.23%) in 1996-99. Despite this increasing workload, no additional resources have yet been required in the Breast Screening Unit.1209 cancers (0.57%) were found in the screened population, and there were no screen detected cancers in the implant group, and there was no significant difference between the groups. CONCLUSIONS: As the number of younger women receiving breast implants continues to rise, when they become eligible for the National Health Service Breast Screening Programme (NHSBSP), departments should be aware that additional personnel and finance will be needed.

Breast Implants↗
PubMed1997

Changing attitudes towards breast-conserving treatment of early breast cancer in the south-eastern Netherlands: results of a survey among surgeons and a registry-based analysis of patterns of care.

To see whether personal preferences of surgeons can explain the trends in the use of breast-conserving therapy (BCT) of early breast cancer, questionnaires were sent to the surgeons of seven community hospitals in the south-eastern Netherlands in 1987 and 1995. The answers were set against the actual use of breast-conserving therapy in the hospitals in the period 1984-94, as monitored by the Eindhoven Cancer Registry. The proportion of surgeons who were willing to use BCT for tumours < or =3 cm increased from 43% in 1987 to 93% in 1995. In 1995, the majority of the surgeons considered multicentric tumour growth, diffuse microcalcifications on the mammogram and an extensive intraductal component around the tumour as contraindications for breast-conserving therapy. The proportion of patients with an operable, non-metastasized breast tumour of < or =5 cm in diameter undergoing breast-conservative surgery increased from 31% in 1984 to 60% in 1989 (P<0.01) and remained at that level in 1990 and 1991. Between 1991 and 1993, the proportion receiving breast-conservative surgery decreased significantly for patients younger than 50 years and a tumour 2.1-3.0cm in diameter, and also for those 50-69 years old with a tumour < or =2.0cm or 3.1-5.0cm across. The observed decrease in BCT in the south-eastern Netherlands in some subgroups seems to reflect the growing awareness of potential risk factors for local recurrence following BCT.

Adult↗
PubMed2002

Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients.

Conventional radiotherapy after breast-conserving therapy is confined to 50-55 Gy external beam radiation therapy (EBRT) to the whole breast and 10-16 Gy external boost radiation to the tumour bed or brachytherapy to the tumour bed. Local recurrence rate after breast-conserving surgery varies between 5 and 18%. External boost radiation can partially miss the tumour bed and therefore can result in local failure. Intra-operative radiotherapy (IORT) as a high precision boost can prevent a 'geographical miss'. From October 1998 to December 2000, 156 patients with stage I and stage II breast cancer were operated upon in a dedicated IORT facility. After local excision of the tumour, the tumour bed was temporarily approximated by sutures to bring the tissue in the radiation planning target volume. A single dose of 9 Gy was applied to the 90% reference isodose with energies ranging from 4 to 15 MeV, using round applicator tubes 4-8 cm in diameter. After wound healing, the patients received additional 51-56 Gy EBRT to the whole breast. No acute complications associated with IORT were observed. In 5 patients, a secondary mastectomy had to be performed because of tumour multicentricity in the final pathological report or excessive intraductal component. 2 patients developed rib necroses. In 7 patients, wound healing problems occurred. After a mean follow-up of 18 months, no local recurrences were observed. Cosmesis of the breast was very good and comparable to patients without IORT. Preliminary data suggest that IORT given as a boost after breast-conserving surgery could be a reliable alternative to conventional postoperative fractionated boost radiation by accurate dose delivery and avoiding geographical misses, by enabling smaller treatment volumes and complete skin-sparing and by reducing postoperative radiation time by 7-14 days.

Adult↗
PubMed2002

Aromatase and prostaglandin inter-relationships in breast adipose tissue: significance for breast cancer development.

The role of prostaglandins in the development of breast cancer is a topic of growing interest. Stimulation of aromatase expression within the breast has been proposed as a mechanism whereby prostaglandins could influence breast cancer growth. In the present study, we show that PGE2 is a powerful stimulator of aromatase expression in human breast adipose stromal cells. Moreover, TNFalpha, which also stimulates aromatase expression in breast adipose stromal cells, acts to increase the secretion of PGE2 by these cells, as well as the expression of COX 2 and PGE synthase, but not that of COX 1. On the other hand, class I cytokines had no effect, either by themselves or in the presence of estradiol. These factors had little influence on secretion of 15-deoxy-delta12, 14-PGJ2, which is inhibitory of aromatase expression by breast adipose stromal cells. These results further substantiate an important role for PGE2 to stimulate estrogen biosynthesis within the local environment of the breast.

Adipose Tissue↗
PubMed2003

hTERT expression in human breast cancer and non-cancerous breast tissue: correlation with tumour stage and c-Myc expression.

Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) gene is the rate-limiting determinant of telomerase reactivation. The present study aims to quantitatively measure the expression of hTERT mRNA in human breast cancer, adjacent non-cancerous tissue (ANCT) and benign breast lesions, examine the association between hTERT and the clinicopathological characteristics of the cancer specimens and to explore the relationship between c-Myc and hTERT expressions. RNA was extracted from 49 breast carcinomas, 46 matched ANCT, and eight fibroadenomas. hTERT and c-Myc mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology. hTERT mRNA was present in all of the cancerous and most of ANCT specimens with levels being much higher in the cancerous tissue than in ANCT. The ratio of hTERT mRNA in tumour to that in ANCT was 2011 (95% confidence interval 373-10,853, P < 0.0001). There was no significant association between tumour hTERT expression and patient's age, tumour size, grade, nodal metastasis, estrogen receptor (ER) positivity, lymphovascular (LVI) or c-Myc expression. However, there was a weak but significant negative correlation between hTERT expression and progesterone receptor (PR) status (p = 0.04) in tumours. hTERT mRNA expression was also significantly higher in carcinomas (median = 2.61 x 10(6)) than in fibroadenomas (median = 424).We conclude that hTERT mRNA expression is significantly higher in human breast cancer than in non-cancerous breast tissue suggesting that hTERT has a potential role in breast cancer diagnosis. The hTERT mRNA levels in tumour do not seem to be associated with the patient's age or advanced tumour stage. Furthermore, hTERT mRNA expression does not correlate with c-Myc mRNA expression in breast cancer.

Breast↗
PubMed1991

Purification and characterisation of a breast-cancer-associated glycoprotein not expressed in normal breast and identified by monoclonal antibody 83D4.

Monoclonal antibody (mAb) 83D4 was generated using formol-fixed paraffin-embedded human breast carcinoma tissue as the immunogen. Previous studies demonstrated that it was reactive with breast carcinoma tissues, but not with normal breast. The antigen identified by mAb 83D4 was detected, using ELISA, in MCF7 breast carcinoma cell line membrane extracts, in primary breast and colon carcinoma tissue extracts and in pleural effusion fluid from patients with metastatic breast cancer. No reactivity with 83D4 was found in either human milk fat globule membranes or skimmed milk. 83D4 reactive antigen was found to be a heterogeneous high molecular weight (MW) protein (apparent Mr:300-400 to over 1000 kDa) by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The antigen was purified from MCF7 cells, breast and colon carcinomas and effusion fluid, by perchloric acid solubilisation followed by immunoaffinity chromatography with 83D4. The immunopurified antigen from MCF7 cells and pleural effusion fluid was further analysed by gel filtration and ion-exchange chromatography, which confirmed the high MW and indicated the charge heterogeneity of the reactive molecules. The 83D4 reactive antigen strongly bound to wheat-germ agglutinin and weakly to peanut lectin. No binding was found with lentil lectin or concanavalin A. Antigenic activity was strongly reduced by trypsin and subtilysin digestion and by treatment with sodium periodate, but it was not affected by neuraminidase. These results imply the glycoprotein nature of the 83D4-defined antigen and the involvement of carbohydrate, but probably not sialic acid, in the epitope. Purified 83D4 antigen did not display reactivity for mAb HMFG-1, directed against a polymorphic epithelial mucin, PEM, using ELISA, but bound mAb CC49 and weakly mAb B72.3, antibodies which define a tumour associated glycoprotein, TAG-72. Moreover CC49 and 83D4 showed similar reactivity pattern in immunoblotting assays. A double determinant radioimmunoassay confirmed that 83D4 antigen carries epitopes for mAb B72.3 and CC49. Competition radioimmunoassays clearly distinguished the 83D4 defined epitope from those recognised by B72.3 and CC49, demonstrating that antibody 83D4 identifies a unique epitope. It is suggested that the antigens identified by mAb 83D4 and by mAb B72.3 and CC49 may form part of the same family of carcinoma associated glycoproteins.

Antibodies, Monoclonal↗