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[Initial results of the Project of the German Breast Cancer Study Group on "Breast saving therapy of the small breast cancer"].

In the German Breast Cancer Study Group (GBSG) multicenter trial "Breast preservation in small breast cancer" 1119 patients were accrued over a period of six years. The study was originally designed as a randomized trial which had to be changed into a prospective observation study. A high therapeutic standard was guaranteed by quality control. The univariate analysis of prognostic variables was the first step to a valid treatment comparison. Those factors determined as being significant were combined with the treatment effects in a multivariate analysis. The published results were obtained after a median observation time of four years.

Breast Neoplasms↗

Breast within a breast: a review of breast hamartomas.

A 22-year-old woman who presented with a large lump in the left breast, subsequently found to be a breast hamartoma, is described. A full review is given of this rare and unusual benign breast lesion, which is likely to be recognised increasingly with the advent of mammographic screening.

Adult↗

[Duct pattern of the breast. An indicator of patients with increased risk of breast cancer development? A histological and mammographic study with 160 cases of breast cancer (author's transl)].

In 1975 John Wolfe proposed a classification of mammographic findings concerning the distribution of the duct pattern to select patients with high cancer risk. In a retrospective study we classified 160 patients with breast cancer according to the duct pattern classification. Our findings support well the results of Wolfe. Type N (normal duct pattern) is found in only 8,9% of all cancer patients whereas breast cancer was combined in 80% with the P2-DY-type. Our investigation confirms the classification of the duct pattern according to Wolfe as a valuable addition to the mammographic diagnosis of breast cancer.

Adult↗

Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.

AIM: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. SETTING: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. METHODS: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. RESULTS: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (kappa=0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. CONCLUSION: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area.

Breast Neoplasms↗

[Fibroadenoma in an accessory breast. A case of polythelia and fibroadenoma in the left breast region and a perivulvar accessory breast].

The case of a 32-year-old female patient with multiple malformations (hare-lip, polythelia, fibroadenoma in an accessory mammary gland) and independent of these, another fibroadenoma in the breast is reported. The fibroadenoma developing in the accessory breast around the vulva, diagnosed by means of aspiration biopsy cytology, should be payed special attention. This case also confirms the applicability in preoperative diagnostics of aspiration biopsy cytology, a method which has proved to be effective for years.

Adenofibroma↗

Prognosis after treatment for loco-regional recurrence after mastectomy or breast conserving therapy in two randomised trials (EORTC 10801 and DBCG-82TM). EORTC Breast Cancer Cooperative Group and the Danish Breast Cancer Cooperative Group.

The aim of this study was to investigate and compare the prognosis after treatment for loco-regional recurrences (LR) after (modified) radical mastectomy (MRM) or breast conserving therapy (BCT), in terms of overall survival and time to subsequent LR, in patients originally treated in two European randomised trials. In EORTC trial 10801 and DBCG trial 82-TM, 1,807 patients with stage I and II breast cancer were randomised to receive MRM or BCT from 1980 to 1989. All patients with a LR in these trials were analysed for survival and time to subsequent LR after salvage treatment. Of these, 133 patients had their LR as a first event, the majority within 5 years after initial treatment. The prognostic significance for survival and time to subsequent LR after salvage treatment was analysed in uni-, and multivariate analyses for a number of original tumour- and recurrence-related variables. After salvage treatment of LR after MRM or BCT, actuarial survival curves and the actuarial locoregional control curves were similar. The 5-year survival rates were 58% and 59% and the 5-year subsequent loco-regional control rates 62% and 63%, respectively. In a multivariate analysis, pN category (P = 0.03), pT category (P = 0.01) and vascular invasion (P = 0.02) of the primary tumour were the only independent prognostic factors for survival, whereas extensive LR (P < 0.001), interval < or = 2 years (P < 0.002) and pN+ at primary treatment (P = 0.004) were significant predictive factors for time to subsequent LR. The type of original treatment (MRM or BCT) did not have any prognostic impact. It is concluded that the survival and time to subsequent LR after treatment for an early loco-regional recurrence after MRM or BCT was similar in these two European randomised trials. This suggests that both after MRM and BCT an early LR is an indicator of a biologically aggressive tumour; early loco-regional relapse carries a poor prognosis and salvage treatment only cures a limited number of patients, whether treated by MRM or BCT originally.

Adult↗

Doxorubicin versus methotrexate both combined with cyclophosphamide, 5-fluorouracil and tamoxifen in postmenopausal patients with advanced breast cancer--a randomised study with more than 10 years follow-up from the Danish Breast Cancer Cooperative Group. Danish Breast Cancer Cooperative Group (DBCG).

To evaluate the substitution of methotrexate with doxorubicin (Dox) in CMF-(cyclophosphamide, methotrexate, 5-fluorouracil) containing regimen for advanced breast cancer, 415 postmenopausal patients below the age of 66 years, naïve to chemotherapy, were accrued from 1980 to 1984 and followed-up until 1995. They received tamoxifen 30 mg daily orally and by randomisation either 400 mg/m2, cyclophosphamide, 25 mg/m2 doxorubicin and 500 mg/m2 5-fluorouracil (CAF) or 40 mg/m2 methotrexate instead of Dox (CMF) intravenously (i.v.) days 1 + 8 repeated every 4 weeks. Dox was substituted by methotrexate at a cumulative dose of 550 mg/m2. Among 341 eligible patients the response rate and median time to progression was significantly in favour of CAF: 53% CAF versus 36% CMF (P = 0.002) and 11.8 months CAF versus 6.5 months CMF (P = 0.001). Median duration of response was 19.5 CAF versus 18.0 CMF months, and survival 20.8 CAF versus 17.4 CMF months (non-significant). The two regimens were equimyelotoxic. There were no treatment-related fatalities but 1 patient with congestive heart failure on CAF was reported. Nausea/vomiting, stomatitis and infections were modest in both groups, whilst alopecia was more common with CAF. Regression analysis showed that long recurrence free interval, good performance status, and no visceral involvement was significantly related to long-term survival, whilst the treatment regimen was not. It is concluded that in chemotherapy-naïve patients with advanced breast cancer Dox-containing regimens are superior and remain the first choice of chemotherapy, especially in patients with visceral metastases, until newer drugs and combinations have been proven to be superior.

Adult↗

Breast MR imaging in women at increased lifetime risk of breast cancer: clinical system for computerized assessment of breast lesions initial results.

The authors developed a clinical system for computerized delineation, rating, and classification of breast lesions depicted in contrast material-enhanced magnetic resonance images obtained in women with increased lifetime risk of breast cancer. Initial results showed negative predictive values above 98% at 50% positive predictive value with negligible interoperator differences. The system demonstrated potential to help exclude malignancy with high confidence and reproducibility with a positive predictive value that is acceptable in screening.

Breast Neoplasms↗

Molecular clonality relationships in initial carcinomas, ipsilateral breast failures, and distant metastases in patients treated with breast-conserving therapy: evidence suggesting that some distant metastases are derived from ipsilateral breast failures and that metastases can metastasize.

We studied the clonality relationships in invasive breast carcinomas, ipsilateral breast failures (IBFs), and distant metastases (DMs) using a polymerase chain reaction-loss of heterozygosity (LOH) clonality assay to determine whether IBFs can be the source of DMs. Six cases of initial carcinomas, IBFs, and DMs were identified. Carcinoma DNA was extracted from paraffin blocks and analyzed with 20 markers. In 2 cases, the LOH pattern suggested the DM directly resulted from the IBF. In 2 cases, the initial carcinoma, IBF, and DM were one progressive, genetically unstable process. Separate subclones in the initial carcinoma gave rise to the IBF and DM in 1 case, and the DM derived from a second IBF in 1 case. The relationships of initial carcinomas, IBFs, and DMs are complex. DMs seem to be the direct result of IBFs in some cases. Some carcinomas seem to be composed of subclones with different and unrelated IBF and DM potential.

Aged↗

Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Scottish Cancer Trials Breast Group and ICRF Breast Unit, Guy's Hospital, London.

There are no previous reports of trials that have directly compared the effects of adjuvant chemotherapy with oophorectomy in premenopausal women with node-positive breast cancer. During 10 years we recruited 332 such women who were randomised, after mastectomy or conservation therapy, to receive either ovarian ablation or cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy, each with or without prednisolone 7.5 mg daily for 5 years. After a maximum follow-up of 12 years, we detected no significant overall differences in relapse rates, or in event-free or total survival for ovarian ablation compared with chemotherapy or for prednisolone versus no prednisolone, nor any suggestion of an interaction between these factors. Actuarial total survival at 8 years was 60% overall, irrespective of treatment, with a hazard ratio and 95% Cl of 1.12 (0.76-1.63) for the comparison of CMF with ovarian ablation and 1.26 (0.86-1.84) for prednisolone versus no prednisolone. Oestrogen receptor (ER) assays were done in 270 (81%) primary tumours but these results played no part in the randomisation procedure. When patient outcome was analysed in relation to the concentration of ER in the tumour, there was a statistically significant interaction between ER content and treatment, such that ovarian ablation was associated with improved survival in patients with ER concentrations 20 fmols/mg protein or more and CMF was more beneficial for patients with values less than 20 fmols/mg protein. No such interaction was seen for prednisolone therapy. Oestrogen receptor content has a role in decisions about treatment for primary breast cancer.

Adult↗

Immediate breast reconstruction in two stages using textured, integrated-valve tissue expanders and breast implants: a retrospective review of 171 consecutive breast reconstructions from 1989 to 1996.

A 7-year experience with 171 consecutive immediate breast reconstructions by one surgeon using a textured integrated-valve tissue expander was reviewed. All patients were reconstructed in multiple stages using a temporary biodimensional tissue expander followed months later by a long term implant. There was one (0.6 percent) spontaneous expander deflation that was replaced. Two (1.2 percent) expanders were removed for infection, and one was removed electively. Fourteen patients (8 percent) had flaps as well as expanders. Initially, expanders were replaced with silicone gel-filled and round saline-filled implants. Later, expanders were replaced mostly with anatomically designed textured saline-filled implants. Of the 171 expanders, 139 were thus ultimately followed by such anatomic designs. Seven (4 percent) of the implants were replaced because of deflation over 7 years. Five patients were lost to follow-up during the expansion phase of their reconstruction. Thirteen percent of these reconstructions received local radiation either before, during, or after expansion. There were a total of five (2.9 percent) significant capsular contractures, with four of them occurring in radiated patients. Ninety-eight percent of a subgroup of 42 consecutively queried patients expressed satisfaction with their reconstruction, while only 2 percent of the queried patients were dissatisfied.

Breast Implants↗

Are breast density and bone mineral density independent risk factors for breast cancer?

BACKGROUND: Mammographic breast density and bone mineral density (BMD) are markers of cumulative exposure to estrogen. Previous studies have suggested that women with high mammographic breast density or high BMD are at increased risk of breast cancer. We determined whether mammographic breast density and BMD of the hip and spine are correlated and independently associated with breast cancer risk. METHODS: We conducted a cross-sectional study (N = 15,254) and a nested case-control study (of 208 women with breast cancer and 436 control subjects) among women aged 28 years or older who had a screening mammography examination and hip BMD measurement within 2 years. Breast density for 3105 of the women was classified using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) categories, and percentage mammographic breast density among the case patients and control subjects was quantified with a computer-based threshold method. Spearman rank partial correlation coefficient and Pearson's correlation coefficient were used to examine correlations between BI-RADS breast density and BMD and between percentage mammographic breast density and BMD, respectively, in women without breast cancer. Logistic regression was used to examine the association of breast cancer with percentage mammographic breast density and BMD. All statistical tests were two-sided. RESULTS: Neither BI-RADS breast density nor percentage breast density was correlated with hip or spine BMD (correlation coefficient = -.02 and -.01 for BI-RADS, respectively, and -.06 and .01 for percentage breast density, respectively). Neither hip BMD nor spine BMD had a statistically significant relationship with breast cancer risk. Women with breast density in the highest sextile had an approximately threefold increased risk of breast cancer compared with women in the lowest sextile (odds ratio = 2.7, 95% confidence interval = 1.4 to 5.4); adjusting for hip or spine BMD did not change the association between breast density and breast cancer risk. CONCLUSION: Breast density is strongly associated with increased risk of breast cancer, even after taking into account reproductive and hormonal risk factors, whereas BMD, although a possible marker of lifetime exposure to estrogen, is not. Thus, a component of breast density that is independent of estrogen-mediated effects may contribute to breast cancer risk.

Adult↗

Reconstructive management of contralateral breast cancer in patients who previously underwent unilateral breast reconstruction.

When a patient who has had unilateral breast reconstruction presents with a new cancer on the opposite side, the reconstructive management of the second breast can be unclear. This study was performed to determine whether reconstruction of the second breast is oncologically reasonable and to evaluate the reconstructive options available to these patients. Patients who had mastectomy with unilateral breast reconstruction between 1988 and 1994 and who had a minimal follow-up of 5 years from the initial breast cancer were reviewed. Of 469 patients reviewed, 18 patients (4 percent) were identified who developed contralateral breast cancer. Mean age at the initial breast cancer presentation was 43 years (range, 26 to 57 years), and mean age at presentation with contralateral breast cancer was 48 years (range, 36 to 67). The mean interval between the initial and contralateral breast cancer presentations was 5 years (range, 1 to 10 years). Mean follow-up from the time of contralateral breast cancer was 5 years (range, 1 to 9 years). In most cases, contralateral breast cancer presented at an early stage (13 of 18 patients; 72 percent), and a shift to an earlier stage at presentation of the contralateral cancer was evident compared with the initial breast cancer. Of the 18 patients who developed contralateral breast cancer, 16 (89 percent) had no evidence of disease, one was alive with disease, and one died. Reconstructive management after the initial mastectomy included 16 transverse rectus abdominis myocutaneous flaps (seven free and nine pedicled), one latissimus dorsi myocutaneous flap with implant, and one superior gluteal free flap. Surgical management of the second breast after contralateral breast cancer included breast conservation in two patients, mastectomy without reconstruction in four, and mastectomy with reconstruction in 12. Reconstruction of the second breast included one free transverse rectus abdominis myocutaneous flap, three extended latissimus dorsi flaps, two latissimus dorsi myocutaneous flaps with implants, three implants alone, two Rubens flaps, and one superior gluteal free flap. No major complications were noted after the reconstruction of the second breast. The best symmetry was obtained when similar methods and tissues were used on both sides. The incidence of contralateral breast cancer after mastectomy and unilateral breast reconstruction is low. In most cases, contralateral breast cancer presents at an earlier stage compared with the initial breast cancer, and the prognosis is good. In patients who develop a contralateral breast cancer after mastectomy and unilateral breast reconstruction, the reconstruction of the second breast after mastectomy is oncologically reasonable and should be offered to provide optimal breast symmetry and a better quality of life. The best result is obtained when similar methods and tissues are used on both sides.

Adult↗

Relationship between 18F-FDG uptake and breast density in women with normal breast tissue.

UNLABELLED: Breast density affects the mammographic detectability of breast cancer. The study aimed to evaluate the impact of breast density on the (18)F-FDG uptake of normal breast tissue. METHODS: The study population consisted of 45 women (median age, 54 y; age range, 42-77 y). All underwent whole-body (18)F-FDG PET for various indications other than breast cancer, and all underwent mammography within a mean of 6.6 +/- 4.9 mo of PET. On the basis of mammographic findings, breasts were categorized as extremely dense, heterogeneously dense, primarily fatty, or entirely fatty. Regions of interest were drawn on every PET image in which breast tissue was visualized. Average and peak standardized uptake values (SUVs) were calculated for the left and right breasts. RESULTS: Mammography showed that 20 of the 45 women had heterogeneously dense breasts, 1 had extremely dense breasts, 20 had primarily fatty breasts, and 4 had entirely fatty breasts. In dense breasts, the average SUV was 0.39 +/- 0.05 (right breast) and 0.36 +/- 0.07 (left breast) and the peak SUV was 0.93 +/- 0.16 and 0.89 +/- 0.18, respectively. The average and peak SUVs were significantly lower for primarily fatty breasts than for dense breasts (P < 0.01). Peak and average SUVs of entirely fatty breasts also differed significantly from peak and average SUVs of dense and primarily fatty breasts (P < 0.01). The impact of hormonal status on SUV was significant but less than the impact of breast density. No significant relationship between average SUV or peak SUV and age or serum glucose level was observed. CONCLUSION: Breast density and hormonal status affect the uptake of (18)F-FDG. Dense breasts exhibit, on average, significantly higher (18)F-FDG uptake than do nondense breasts. However, the highest peak SUV observed in dense breasts was 1.39, which is well below the SUV of 2.5 commonly used as a cutoff between benign and malignant tissue. Therefore, breast density is unlikely to affect the ability of (18)F-FDG PET to discriminate between benign and malignant breast lesions.

Adipose Tissue↗

Impact of breast density on computer-aided detection for breast cancer.

OBJECTIVE: Our aim was to determine whether breast density affects the performance of a computer-aided detection (CAD) system for the detection of breast cancer. MATERIALS AND METHODS: Nine hundred six sequential mammographically detected breast cancers and 147 normal screening mammograms from 18 facilities were classified by mammographic density. BI-RADS 1 and 2 density cases were classified as nondense breasts; BI-RADS 3 and 4 density cases were classified as dense breasts. Cancers were classified as either masses or microcalcifications. All mammograms from the cancer and normal cases were evaluated by the CAD system. The sensitivity and false-positive rates from CAD in dense and nondense breasts were evaluated and compared. RESULTS: Overall, 809 (89%) of 906 cancer cases were detected by CAD; 455/505 (90%) cancers in nondense breasts and 354/401 (88%) cancers in dense breasts were detected. CAD sensitivity was not affected by breast density (p=0.38). Across both breast density categories, 280/296 (95%) microcalcification cases and 529/610 (87%) mass cases were detected. One hundred fourteen (93%) of the 122 microcalcifications in nondense breasts and 166 (95%) of 174 microcalcifications in dense breasts were detected, showing that CAD sensitivity to microcalcifications is not dependent on breast density (p=0.46). Three hundred forty-one (89%) of 383 masses in nondense breasts, and 188 (83%) of 227 masses in dense breasts were detected-that is, CAD sensitivity to masses is affected by breast density (p=0.03). There were more false-positive marks on dense versus nondense mammograms (p=0.04). CONCLUSION: Breast density does not impact overall CAD detection of breast cancer. There is no statistically significant difference in breast cancer detection in dense and nondense breasts. However, the detection of breast cancer manifesting as masses is impacted by breast density. The false-positive rate is lower in nondense versus dense breasts. CAD may be particularly advantageous in patients with dense breasts, in which mammography is most challenging.

Adult↗

Identification of distinct protein expression patterns in bilateral matched pair breast ductal fluid specimens from women with unilateral invasive breast carcinoma. High-throughput biomarker discovery.

BACKGROUND: Analysis of the biochemical and cellular contents of breast ductal fluid has recently gained attention as a potential noninvasive method for studying the local microenvironment associated with the development and progression of breast carcinoma. METHODS: Patients with unilateral primary invasive breast carcinoma were eligible for the current prospective pilot study. Nipple aspiration fluid (NAF) was obtained from the breast with cancer and the normal contralateral breast and subjected to two-dimensional electrophoresis. Computer-assisted image analysis was used to analyze NAF protein expression profiles. RESULTS: The number of separate protein spots detected in NAF samples ranged from 1280 to 1649. Substantial qualitative differences were identified between NAF protein expression patterns in the breast with cancer compared with the breast without cancer. Protein spots detected in the breast with cancer and not in the breast without cancer from the same patient varied from 30 to 202 different proteins. In addition, the number of protein spots detected in the breast without cancer and not in the breast with cancer of the same patient varied from 14 to 73 different proteins. Conversely, in an individual without breast carcinoma, only three protein spots were detected in the left breast but not the right breast, and only two were detected in the right breast but not the left breast. CONCLUSIONS: The breast is a unique organ in that its microenvironment can be readily accessed and evaluated by aspiration of fluid from the nipple. Breast ductal fluid contains a large number of proteins. As breasts are paired organs, comparisons of ductal fluid from a breast with cancer and the same patient's normal contralateral breast may reveal significant differences in protein expression associated with breast carcinoma. Recent advances in image analysis, automated mass spectrometry, and bioinformatics have provided the tools necessary to use ductal fluids from breast carcinoma patients for high-throughput biomarker discovery.

Biomarkers, Tumor↗