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.

Differential effects of estrogen on DNA synthesis in human periodontal ligament and breast cancer cells.

BACKGROUND: It is important to clarify the biological function of the female sex hormones estrogen and progesterone in periodontal ligament cells, as these hormones may affect periodontal health. We have previously shown that human periodontal ligament cells express estrogen receptor beta (ERbeta) but not ERalpha, whereas human breast cancer cells (MCF7) express both ERalpha and ERbeta. Data on progesterone receptor (PgR) expression in human periodontal ligament cells have not been reported. OBJECTIVES: Determine PgR expression in human periodontal ligament and MCF7 cells and to investigate how estrogen affects DNA and collagen synthesis in these two cell types showing different pattern of expression for ERalpha and beta. METHODS: Periodontal ligament cells were obtained from the periodontal ligament of premolars extracted for orthodontic reasons and MCF7 cells from the American Type Culture Collection (ATCC). PgR expression was determined by immunocytochemistry. DNA and collagen synthesis was determined by [(3)H]thymidine and L-[(3)H]proline incorporation, respectively. RESULTS: PgR immunoreactivity was observed in nuclei of MCF7 but not periodontal ligament cells. Treatment with estrogen (17beta-estradiol, E(2)) at physiological concentrations for 24 h stimulated DNA synthesis by more than two times in MCF7 cells, whereas there was no effect on periodontal ligament cell DNA synthesis. The ER blocker ICI 182780 fully reversed the stimulatory effect of E(2). Not only short-term (24 h) but also long-term (5 days) treatment with E(2) lacked effect on DNA synthesis in periodontal ligament cells. Neither periodontal ligament cell viability nor collagen synthesis was affected by E(2) treatment. Identical results were observed in periodontal ligament cells from male and female subjects. CONCLUSIONS: Human MCF7 but not periodontal ligament cells express PgR, suggesting that progesterone via PgR affects MCF7 but not periodontal ligament cells. Further, estrogen stimulates breast cancer MCF7 cell proliferation, whereas it has no effect on proliferation of periodontal ligament cells, probably reflecting cell type specific ER expression pattern in these two cell types.

Risk factors for local recurrence after breast-conserving surgery.

BACKGROUND: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. METHOD: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. RESULTS: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. CONCLUSION: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.

Are cellular polarisation and mitotic frequency prognostic factors for local recurrence in patients with ductal carcinoma in situ of the breast?

There is still no generally accepted histopathological classification system for ductal carcinoma in situ (DCIS) of the breast. Nuclear grade, with or without other histopathological parameters (i.e. comedo-type necrosis and cellular polarisation), has been demonstrated to yield prognostic information. A detailed method for the evaluation of the mitotic frequency in DCIS, based on an approach by Contesso, was used in this study. We also investigated if cellular polarisation and mitotic frequency were important for the ipsilateral local recurrence-free interval (IL-RFI) in 121 DCIS patients who had been operated upon with breast-conserving treatment (BCT) without radiotherapy. Both cellular polarisation and the mitotic frequency were associated with histopathological and cellular biological factors (in previous evaluations), and were of borderline significance for IL-RFI in the univariate analyses. However, when nuclear grade was included in the multivariate analyses (with or without the growth pattern), neither cellular polarisation nor the mitotic frequency were of any independent prognostic value.

Histopathological and cell biological factors of ductal carcinoma in situ before and after the introduction of mammographic screening.

With the introduction of mammographic screening the incidence of ductal carcinoma in situ (DCIS) has increased to 10-15% of all breast cancers. The aim of this study was to investigate whether there were any morphological and cell biological differences between DCIS detected during the pre-screening (n = 39) as opposed to the screening period (n = 120). We could not demonstrate any statistically significant differences between the pre-screening and the screening period with regard to nuclear grade, presence of necrosis, the Van Nuys classification system, growth pattern, or cell biological factors (estrogen and progesterone receptors, c-erbB-2, p53, DNA ploidy status, Ki67, and Auer classes). These findings suggest that DCIS tumors detected during the two time periods have a similar malignant potential. DCIS detected during the screening period was further divided into the prevalence period versus the period thereafter, and symptomatic versus screening-detected asymptomatic cases. More cases with diffuse growth patterns were seen during the prevalence period than after the prevalence period, and screening-detected asymptomatic DCISs were more often 15 mm or smaller in diameter than DCISs detected symptomatically.

Cell biological factors in ductal carcinoma in situ (DCIS) of the breast-relationship to ipsilateral local recurrence and histopathological characteristics.

All cases of ductal carcinoma in situ (DCIS) diagnosed from 1987 to 1991 in the Southern Health Care Region of Sweden, and operated upon with breast conserving treatment (BCT) with (n=66) or without (n=121) postoperative radiation (RT) were clinically followed, morphologically re-evaluated and analysed for cell biological factors (immunohistochemical assays or DNA flow cytometry). Median age at diagnosis was 58 years (range 29--83 years) and median follow-up was 62 months. Oestrogen (ER)- and progesterone receptor (PR)-negativity, c-erbB-2 overexpression, low bcl-2 expression, p53 accumulation, DNA non-diploidy and high Ki67, were strongly associated with high grade DCIS, and comedo-type necrosis. In contrast, significant associations to growth pattern (not diffuse versus diffuse) were seen only for c-erbB-2 and PgR. There was also a strong relationship between the cell biological factors, and a summary cell biological index based on principal component analysis was introduced (CBI-7). In the group that had not received postoperative RT, 31 ipsilateral local recurrences occurred (13 invasive, 18 DCIS). Ipsilateral recurrence-free interval (IL-RFI) was in univariate analyses significantly, or almost significantly, shorter for patients showing p53 accumulation, high Ki67 or low bcl-2, compared with patients with normal p53, low Ki67 and high bcl-2. The prognostic importance of the remaining cell biological factors was less pronounced. On the other hand, the index CBI-7, was a strong predictor for recurrence.

S-phase fraction and urokinase plasminogen activator are better markers for distant recurrences than Nottingham Prognostic Index and histologic grade in a prospective study of premenopausal lymph node-negative breast cancer.

PURPOSE: Histologic grade, Nottingham Prognostic Index (NPI), estrogen receptor (ER) and progesterone receptor (PgR) status, and tumor size have previously been shown to be important prognostic indicators for distant recurrence of breast cancer. The purpose of this study was to compare the prognostic value of these factors with flow cytometric S-phase fraction (SPF), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1) in premenopausal patients with lymph node-negative breast cancer. PATIENTS AND METHODS: In 237 consecutive premenopausal patients with lymph node-negative breast cancer and freshly frozen tumor material available, SPF, ER and PgR status, uPA and its inhibitor PAI-1, histologic grade, and NPI were evaluated. RESULTS: SPF was univariately the most powerful prognostic factor for distant recurrence, followed by uPA, histologic grade, PgR, age, ER, NPI, and PAI-1, the latter being nonsignificant. Multivariate analysis revealed that neither NPI nor histologic grade was significant after adjustment for SPF, a fact that may be explained by the strong association between these factors. uPA was, however, an independent prognostic factor in addition to SPF, NPI, or histologic grade. CONCLUSION: In this prospective study, SPF and uPA were found to be independent prognostic factors in premenopausal women with lymph node-negative breast cancer. We suggest that SPF, if performed under standardized conditions, can replace histologic grade as a selection instrument for adjuvant medical treatment. The value of the combination of SPF and uPA needs to be confirmed in an independent prospective trial.

Immunocytochemical demonstration of oestrogen receptor beta in blood vessels of the female rat.

The role of oestrogen receptor (ER) beta in vascular function remains unclear. With the use of a specific ERbeta antibody we have now, using immunocytochemistry, visualized ERbeta in different parts of the vascular tree. In about 70% of medial smooth muscle cells of female rat aorta, tail artery and uterine artery, nuclear immunoreactivity to ERbeta was observed. In these vessels endothelial cells also expressed ERbeta. Vascular expression of the ERalpha subtype was lower than that of ERbeta. In aorta and tail artery, no immunoreactivity towards ERalpha was observed, while in uterine vessels occasional medial smooth muscle and endothelial cells expressed this ER subtype. ERbeta and alpha expression in uterine vessels was independent of the stage of the oestrous cycle, suggesting that variations in uterine blood flow occurring during the cycle are independent of ER density. The regional distribution of ERalpha, as determined by immunocytochemistry, was supported by measurements of ERalpha levels by enzyme immunoassay. In the uterine artery, the level of ERalpha was several times higher (P<0.001) than that of aorta and tail artery (10.1+/-1.7 fmol/mg protein in the uterine artery vs 3.3+/-1.0 and 0.5+/-0.5 fmol/mg protein in aorta and tail artery respectively). Thus, a prominent nuclear expression of ERbeta was observed in the vascular wall of several parts of the vascular tree, while ERalpha predominantly was expressed in uterine vessels, suggesting that ERbeta and alpha may have different roles in vascular function.

Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast.

METHOD AND RESULTS: A standardized histopathological protocol has been designed, in which different histological characteristics of ductal carcinoma in situ (DCIS) are reported: nuclear grade (ng), growth pattern according to Andersen et al., necrosis, size of the lesion, resection margins and focality. Using this protocol a re-evaluation of a population-based consecutive series of 306 cases of DCIS has been done as well as a thorough clinical follow-up. After a median follow-up of 63 months, 13% have developed ipsilateral local recurrences, invasive and/or in situ. Ipsilateral local recurrence-free survival (IL-RFS) was significantly better for patients operated with mastectomy (ME) or breast conserving therapy (BCT) with radiotherapy (RT) than for patients operated with BCT without RT (5-year IL-RFS 96% vs 94% vs 79%, P<0.001). In the subgroup of BCT without RT there were significant differences in IL-RFS between histopathological subgroups: ng 1 + 2 (non-high grade) vs ng 3 (high grade; P=0.014), non-high-grade without comedo-type necrosis vs non-high-grade with comedo-type necrosis vs high-grade (the Van Nuys classification system; P=0.025). Growth pattern (not diffuse vs diffuse) and margins (free vs involved or not evaluated) showed a tendency (P=0.07 and 0.05, respectively) to be associated to IL-RFS. In contrast, no significant differences in IL-RFS were found in subgroups based on mode of detection, focality or size. Ninety-four per cent of the local recurrences after BCT appeared at the previous operation site. CONCLUSIONS: In the BCT without RT group, combinations of either non-high grade and not a diffuse growth pattern or non-high grade and free margins identified groups (constituting approximately 30% of the patients) were at low risk of developing ipsilateral recurrences (6-10%), compared to a 31-37% recurrence risk in the remaining groups during the observed follow-up time. The beneficial effect of post-operative RT for these low-risk groups can be questioned, and should be studied further.

Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group.

Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.

Different patterns of chromosomal imbalances in metastasising and non-metastasising primary breast carcinomas.

In an attempt to identify chromosomal abnormalities that may be associated with a metastatic phenotype, we investigated the pattern of chromosomal gains and losses in 66 node-positive and 63 node-negative primary breast carcinomas. For both subgroups of tumours, losses were more common than gains and the losses were most often the result of structural aberrations. The exceptions were the long arm of chromosome 1, and chromosomes 7, 8, 12, 18 and 20, which were more often gained than lost. Node-negative tumours were preferentially characterised by loss of 6q10-21 and loss of 16q, whereas loss of chromosome 18 was significant for node-positive tumours. Other aberrations that tended to be associated with one of the phenotypes, though not statistically significant, were gain of chromosome 18 and loss of chromosome 10 in node-negative tumours, and gain of chromosome 14 and loss of 12p in node-positive tumours. Our data show that there are differences among the genetic lesions present in node-negative and node-positive breast tumours. Int. J. Cancer (Pred. Oncol.) 84:370-375, 1999.

Multiple polysomies in breast carcinomas: preferential gain of chromosomes 1, 5, 6, 7, 12, 16, 17, 18, and 19.

Chromosome G-banding analysis of metaphase cells from 16 primary breast carcinomas revealed the presence of multiple polysomies in near-diploid as well as in polyploid cells. Chromosome 17 was preferentially gained in 7 tumors, followed in frequency by chromosomes 1, 12, and 19 (5 tumors each), and chromosomes 5, 6, 7, 16, and 18 (4 tumors each). Eleven of the 16 carcinomas had, apart from the clones exhibiting the numerical gains, other unrelated clones. Nine of these 11 cases had clones with structural chromosome aberrations, 5 of which had structural aberrations involving the short arm of chromosome 3. The biologic significance, if any, of this seemingly nonrandom coexistence of multiple polysomies with structural aberrations of 3p is at present not known. The pattern of numerical chromosome aberrations observed in the present study is comparable to previous results from fluorescence in situ hybridization (FISH) studies, with the use of centromeric probes on interphase cells. However, unlike FISH studies, which have been focused on chromosomes 1, 3, 7, 8, 11, 16, and 17, the cytogenetic results reveal that other chromosomes also may be nonrandomly gained as part of multiple polysomies in breast carcinomas. In addition, the tumors with multiple polysomies were generally of high histologic grade and with metastasis to axillary lymph nodes, suggesting that multiple wholechromosome gains may be a pathway of genetic evolution or progression or both in some breast carcinomas.

Cytogenetic changes in benign proliferative and nonproliferative lesions of the breast.

Cytogenetic analysis of short-term cultures from 69 cases of fibrocystic breast changes and 10 samples of normal mammary tissue revealed clonal chromosome aberrations in six fibrocystic lesions. All the histologically normal tissue samples had a normal karyotype. The frequency of cytogenetically abnormal cases seems to correlate with the degree of histopathologic changes of the tissue; nonproliferative lesions may have clonal chromosome alterations, but at a low frequency. Whether women with karyotypically altered fibrocystic "disease" have a higher risk of developing invasive breast cancer, compared with women without microscopically visible genetic anomalies in fibrocystic lesions, remains unknown.

Psychological profile related to malignant tumours of different histopathology.

In a previous preoperative study of patients with gliomas, we made the original observation that patients with high grade as opposed to those with low-grade gliomas have a psychological profile marked by extreme emotional reactivity. In this postoperative study of the psychological profiles of patients with breast cancer, the main funding was unexpectedly analogous with the findings in the brain tumour study. The patients with poorly differentiated ductal carcinomas showed a specific and, compared to the patients with well differentiated carcinomas, outstanding psychological profile marked by extreme emotional reactivity as well as by genuine creativity. Some of the present patients with well differentiated carcinomas showed personality profiles marked by compulsive inhibition, also described earlier in the literature of patients with breast cancer. The psychobiological relations between emotional reactivity and aggressiveness of tumour growth are discussed.

Cytogenetic findings in invasive breast carcinomas with prognostically favourable histology: a less complex karyotypic pattern?

Seventeen invasive primary breast carcinomas of histological types usually considered to be prognostically favourable (2 medullary, 3 papillary, 3 tubular, and 9 mucinous carcinomas) were analysed as part of an ongoing study of the cytogenetics of breast cancer. Thirteen of the tumours (7 mucinous, 2 medullary, 2 papillary, and 2 tubular carcinomas) showed clonal chromosome aberrations. Trisomy 7 and i(1q) were present as sole and recurrent aberrations in the mucinous tumours. The 2 tubular carcinomas and I papillary carcinoma had simple numerical changes only, whereas the second papillary tumour had a balanced translocation as the sole anomaly. Both medullary carcinomas had chromosome numbers in the triploid range, with clones displaying structural and numerical changes. Our data, especially when collated with information on previously published cases of mucinous, papillary, tubular, and medullary breast carcinomas, show that the former 3 histological types, in keeping with their recognised prognostic advantage, appear to exhibit relatively simple karyotypic changes, i.e., numerical aberrations, balanced translocations, and near-diploid chromosome numbers. Medullary carcinomas on the other hand, appear to have more complex karyotypes, similar to those described for the more common ductal and lobular subtypes of breast carcinoma.

Proliferative index obtained by DNA image cytometry. Does it add prognostic information in Auer IV breast cancer?

OBJECTIVE: To investigate whether the S + G2/M fraction (proliferative index) is a prognostic determinant in breast cancers classified as Auer IV. STUDY DESIGN: Prognostic evaluation of Auer IV DNA histograms with respect to the high versus low S + G2/M fraction, obtained by image cytometry on consecutive breast cancer imprint preparations. RESULTS: When studying recurrence-free survival (n = 136), the prognostic value of S + G2/M was found to vary with time: it was negligible before the median time to relapse (1.5 years) but thereafter statistically significant, in both univariate and multivariate analysis. The same pattern was found when overall survival was used as the end point; the effect was delayed to about the median time until death (three years). Tumors with a low S + G2/M fraction were smaller and more often estrogen receptor- and progesterone receptor-positive than those with a high S + G2/M fraction. CONCLUSION: According to ICM-DNA values corresponding to the S + G2/M region, patients with breast cancers classified as Auer IV can be divided into subgroups with different tumor characteristics and prognoses.

Clinical multi-colour fluorescence imaging of malignant tumours--initial experience.

PURPOSE: The detection of malignant tumours relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. MATERIAL AND METHODS: A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents, such as haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 h prior to the study. The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s, was mixed with a normal colour video image of the tissue. RESULTS: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. CONCLUSIONS: The initial clinical experience of using multi-colour fluorescence imaging has shown that the technique has the potential to reveal malignant tumour tissue, including non-invasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.

Tumour biological features of BRCA1-induced breast and ovarian cancer.

BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison group of stage II breast cancers were studied with regard to histopathological features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often DNA non-diploid, as well as being characterised by higher S-phase fraction values. These results suggest that BRCA1-induced breast cancers may manifest distinct tumour biological features of clinical importance.

Karyotypic abnormalities in fibroadenomas of the breast.

Short-term cultures of 50 fibroadenomas of the breast were cytogenetically analyzed. Nine tumors were found to display clonal chromosome aberrations. One had multiple, cytogenetically unrelated clones, whereas the others had a single abnormal clone each. Four cases had one balanced translocation as the sole anomaly, and one had a complex intrachromosomal rearrangement of chromosome 3, leading to loss of 3p material. One fibroadenoma had a single numerical aberration, and one had supernumerary ring chromosomes. The remaining 2 cases had both numerical and structural aberrations. The only recurrent alterations were trisomy 20 and rearrangement of chromosome arm 1p. The finding of similar chromosomal aberrations in fibroadenomas and carcinomas suggests that women with karyotypically abnormal fibroadenomas may have an increased risk of developing subsequent breast cancer. If so, different chromosome anomalies might have different pathogenetic and/or prognostic significance.