The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial.

BACKGROUND: We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment. METHODS: The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety. RESULTS: In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07). CONCLUSION: Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.

Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients.

AIM: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. PATIENTS AND METHODS: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. RESULTS: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. CONCLUSIONS: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.

[Early experience with the advanced breast biopsy instrumentation system in a multicentre study]. / Zwischenbericht über die Anwendung des 'Advanced Breast Biopsy Instrumentation'- Systems im Rahmen einer Multizenterstudie.

Early Experience with the Advanced Breast Biopsy Instrumentation System in a Multicentre Study In an Austrian multicentre trial between September 1998 and December 2001, 474 procedures were performed with the Advanced Breast Biopsy Instrumentation (ABBI), and 389 were entered in the protocol. For reasons of patient comfort, radiological accuracy and low complication rate, the stereotactic excision biopsy with the ABBI system is a useful alternative to 'open' biopsy of non-palpable breast lesions, although there are technical limitations. The question of the therapeutic option in breast cancer cannot be answered yet.

Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Identification of women with early breast cancer by analysis of p43-positive lymphocytes.

Regular screening mammographies and increasing knowledge of high-risk groups have resulted in an improvement in the rate of detection of smaller malignant lesions. However, uncertain minimal mammographic features frequently require further costly and often uncomfortable investigation, including repeat radiological controls or surgical procedures, before cancerous lesions can be identified. Placental isoferritin (p43), a protein with immunosuppressive effects, has been detected on the surface of lymphocytes taken from peripheral blood in patients with breast cancer. In this study we evaluated the sensitivity and specificity of the expression of p43-positive lymphocytes as a marker in early stage breast cancer and also investigated its expression on T-cell subpopulations. The presence of p43-positive lymphocytes was investigated using the monoclonal antibody CM-H-9 and flow cytometry in 76 women with controversial, non-palpable mammographic findings who were undergoing surgical biopsy. Patients with early breast cancer (n = 48) had significantly higher p43-positive cell values (median 3.83%, range 0.98-19.4) than patients with benign lumps (n = 28, median 1.43%, range 0.17-3.7) or controls (n = 22, median 1.3%, range 0.4-1.87) (P < 0.0001). At a cut-off level of 2% p43-positive cells a sensitivity of 91.7% and a specificity of 89.3% for detection of breast cancer could be reached. While the median ratio of total CD4+/CD8+ cells was 2.6, a ratio of 1.3 was found for the p43-positive subpopulation (P < 0.001), thus indicating a significant link between p43 and CD8+ cells. The determination of p43-positive lymphocytes in peripheral blood could serve as an additional diagnostic tool in patients with controversial mammographic findings and could also reduce the need for cost-intensive and often uncomfortable management of these patients.

Effect of interferon alpha-2a on hormone receptor status in patients with advanced breast cancer.

The aim of this study was to assess the effect of recombinant interferon alpha-2a (rh-IFN) on estrogen (ER) and progesterone (PR) receptor expression in patients with advanced breast cancer and the evaluation of the effect of rh-IFN pretreatment on response to endocrine therapy with tamoxifen (TAM). Between June 1990 and November 1992, 20 patients with disseminated breast cancer and with metastatic skin nodules suitable for biopsy were entered into this study. Eighteen assessable patients underwent biopsy before and 2 weeks after treatment with rh-INF. rh-INF 3 x 10(6) IU were administered subcutaneously per day. Patients with ER expression at second biopsy were subsequently treated with 20 mg TAM daily. One patient had rapid disease progression and died before rebiopsy could be performed, and an additional patient refused second biopsy. All other patients were considered assessable. Thirteen patients showed ER expression before rh-IFN treatment, and 5 PR presented with expression. Rh-IFN increased ER expression in three patients and PR in four patients. No change was observed in 8 patients for ER and in 12 patients for PR. ER expression decreased in seven patients and PR expression decreased in two patients, respectively. Two patients showed a partial remission after subsequent treatment with TAM. Adverse reactions caused by rh-IFN were mainly flu-like symptoms. In this trial we found no systematic impact of rh-IFN on hormone receptor expression and, subsequently, on the response rate in patients with advanced breast cancer.

Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations.

The aim of this study was to evaluate the prevalence of simple sequence variation in the BRCA2 gene. To this end, 71 breast and breast-ovarian cancer (HBC/HBOC) families along with 95 control individuals from a wide range of ethnicities were analyzed by means of denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis. In the coding (10 257 bp) and non-coding (2799 bp) sequences of BRCA2, 82 sequence variants were identified. Three different, apparently disease-associated BRCA2 mutations were found in six HBC/HBOC families (8%): two splice site mutations in introns 5 and 21, and one frameshift mutation in exon 11. In the coding region, 53 simple sequence variants were found: 35 missense mutations, one 2 bp deletion (CT) resulting in a stop at codon 3364, one nonsense mutation with a stop at codon 3326, one deletion of a complete codon (AAA) resulting in the loss of leucine, and 15 silent mutations. In the non-coding region, 26 polymorphisms were detected. Of the 79 sequence variants that were not obviously disease-associated, eight were detected only in HBC/HBOC families. The remaining 71 variants were identified in both HBC/HBOC families and control individuals. Sixty three sequence variants (80%) were specific for a continent. Forty two percent (33 out of 79) of the sequence variants were detected exclusively in Africa, though only 13% of the 332 chromosomes screened were of African origin. Our data indicate that, in BRCA2, simple sequence variation is frequent [in the coding region 1 in 194 bp (straight theta = 2.2 x 10(-4)), and in the non-coding region 1 in 108 bp (straight theta = 4.4 x 10(-4)), respectively].

Comparison of immunohistochemical and biochemical measurement of steroid receptors in primary breast cancer: evaluation of discordant findings.

Tumor samples of 240 patients with primary breast cancer were biochemically and immunohistochemically investigated for estrogen receptors (ER) and, in 130 of the samples, for progesterone-receptors (PgR) in order to examine reasons for discordant findings. The biochemical (DCCA) and immunohistochemical assays (ICA) yielded positivity in 71% for ER, and in 44% for PgR. Concordant ER-DCCA and ER-ICA results were obtained in 84%; two thirds of the discordant ER-findings manifested as DCCA-neg/ICA-pos. Concordance in the case of PgR amounted to 72%, and of the discordances 60% were DCCA-neg/ICA-pos. Significant association with postmenopausal status existed only for ER positivity in ICA (p = 0.01), whereas ER-DCCA, PgR-DCCA and PgR-ICA were all more or less independent of the menopausal status. The frequency of discordances was independent of menopausal status. Discordance for ER-assays increased significantly near the respective cut-off point; this was not unequivocally true for PgR-assays. The correlation of tumor types of sparse cellularity, as well as prominent stroma content ('scirrhous carcinoma') with increased frequency of the constellation DCCA-neg/ICA-pos was of borderline significance for PgR (p = 0.06), but not for ER. The percentage of discordant ER-findings, figuring as DCCA-neg/ICA-pos, was statistically significantly increased in locally advanced breast cancer (p = 0.03). Fibrocystic disease in peritumoral breast tissue had no impact on receptor-assay discordance. In any case, the models derived from theoretical thought, laboratory data and singular observations can only in part explain the discordance in steroid receptor values measured with different methods.

Dose intensification of epidoxorubicin and cyclophosphamide in metastatic breast cancer: a randomised study with two schedules of granulocyte-macrophage colony stimulating factor.

A randomised phase II/III study was conducted in patients with advanced breast cancer to determine the dose intensity achievable through an acceleration of administration of chemotherapy with epidoxorubicin and cyclophosphamide (EC) alone, as compared with the combination of this regimen with two different schedules of granulocyte-macrophage colony stimulating factor (GM-CSF). 73 patients received EC intravenous (i.v.) (epidoxorubicin 100 mg/m2, cyclophosphamide 600 mg/m2) on day 1 (group A), or the same chemotherapy plus sub-cutaneous (s.c.) GM-CSF (5 micrograms/kg/day) either from days 3 to 12 (group B) or from days -6 to -3 (group C). The primary objective of the study was the investigation of dose intensity delivered in the three treatment arms, whereas the secondary objective was response rate. A significant increase (P = 0.006) in dose intensity of 21% was observed for treatment group B, whereas the increase in dose intensity achieved in group C (7%) was not significant (P = 0.086). Response rates (complete response (CR) + partial response (PR)) of 56% were observed in group A, 65% in group B, and 57% in group C, respectively. This difference in response rates did not reach statistical significance (P = 0.271). We thus conclude that an acceleration of the EC regimen over the standard schedule could be accomplished with postchemotherapeutic GM-CSF support, leading to an increase in dose intensity, whereas pretherapeutic short-term GM-CSF administration did not reach this goal.

Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.

A randomised clinical trial was performed to test whether or not low-dose chemotherapy lasting only 35 days improves the outcome of breast cancer patients with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR-). Between 1984 and 1990, 277 stage I breast cancer patients with tumours negative for both oestrogen and progesterone receptors were randomised to receive either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for tumour stage, type of surgery, menopausal status and participating centre. Results were analysed both by univariate and multivariate statistical. After a median length of follow-up of 84 months, disease-free (DFS) and overall survival (OS) did not differ significantly between patients having received adjuvant chemotherapy and the control group. Uni- and multivariate analysis did not show any significant prognostic or therapy related factor. A low-dose short-term adjuvant chemotherapy is insufficient to improve the prognosis of patients with breast cancer stage I with ER-, PgR-tumours.

[Therapy studies of the Austrian Breast Cancer Group (ABC)]. / Die Therapiestudien der Austrian Breast Cancer Group (ABC).

The Austrian Breast Cancer Group (ABC) consisting of more than 60 participating centers in Austria has randomized more than 5800 patients in 11 randomized trials since 1984. At present, roughly 30% of all patients with the diagnosis primary breast cancer are accrued in protocols throughout the country. Due to specific activities, the breast conservation rate raised from an initial 20% to more than 60% in the last years. Multicenter trials are not only the basis for progress in medicine but also tools for quality control and quality improvement.

Male breast cancer: Austrian experience.

Data were collected on 169 men treated for breast cancer at 36 surgical departments in Austria between 1970 and 1991. We report here several of their clinical features and assess the importance of established prognostic factors. After a median observation period of 51 months 60 patients (35%) suffered a recurrence. The estimated 5-year recurrence-free survival for the entire group was 55%, and the estimated 5-year overall survival was 62%. Although stage-adjusted data are comparable to those for female breast cancer, the outcome in this series may be attributed to a relatively high frequency of advanced tumor stages. Tumor size (recurrence-free survival p = 0.00001; overall survival p = 0.03) and axillary lymph node status (recurrence-free survival p = 0.0001; overall survival p = 0.0001) proved to have a prognostic impact. Using a multivariate analysis, axillary lymph node status (recurrence-free survival p = 0.001; overall survival p = 0.01) still had prognostic influence. The various procedures used had no effect on local recurrence.

A prospective analysis of immunohistochemically determined hormone receptors and nuclear features as predictors of early recurrence in primary breast cancer.

The immunohistochemically determined receptor status, as well as first-generation risk factors (tumor size, lymph node status, histologic grading including subfactors, tumor histology, and biochemically determined receptor status) were prospectively analyzed in 288 cases of primary breast cancer for their impact on recurrence-free survival (RFS) and overall survival (OS) after a median observation period of 41 months. Immunohistochemically (ER-ICA) and biochemically determined estrogen receptors (ER-DCC), as well as tumor size, lymph node status, histologic grading, mitotic rate, and nuclear polymorphism, were of prognostic value for recurrence-free survival and/or overall survival. In multivariate analysis, lymph node status, tumor size, and mitotic rate proved to be independent prognosticators; ER-ICA showed significance in the univariate analysis which dropped, however, when multivariate analysis was applied. The prognostic power of histologic grading in our series seemed to depend mainly on the subfactors which relate to nuclear features.

Flushable exo-endodrainage: a modified palliative approach to non-resectable malignant biliary obstruction.

The introduction of new imaging techniques has markedly improved the diagnosis of hepatobiliary disorders. Due to their anatomic situation, a substantial percentage of malignancies located near the hilus is not suitable for surgical management. We discuss an effective palliative intervention to relieve jaundice. In many instances drainage is a superior choice when biliodigestive anastomoses are not technically feasible and palliative resection carries a high complication rate. We present an irrigatable exo-endodrainage method employing a modified port-a-cath system as a new alternative. In four patients, all older than 75 years, this system was implanted because of jaundice due to unresectable malignant stenosis of the extrahepatic bile duct. One patient (80 years old) died of pre-existing acute necrotizing pancreatitis, although hyperbilirubinemia was found to decrease on the 7th postoperative day. The other three patients showed complete normalization of their bilirubin levels and their port-a-cath systems remained open until their death (at 3 weeks, 6 months and 7 months respectively).

Immunohistochemical and biochemical measurement of estrogen and progesterone receptors in primary breast cancer. Correlation of histopathology and prognostic factors.

OBJECTIVE: The authors investigated correlations of estrogen-receptor and progesterone-receptor with conventional risk factors as well as histopathology in patients with primary breast cancer. SUMMARY BACKGROUND DATA: Immunohistochemically determined hormone receptors have gained importance as prognosticators in primary breast cancer, but their definitive role has not yet been evaluated. METHODS: Tumor samples from 299 patients were examined for estrogen and progesterone receptors by biochemical and immunohistochemical assay. Correlations with established risk factors (tumor size, lymph node status, menopausal status, grading including subfactors) and histopathology were analyzed. RESULTS: The estrogen receptor, determined by immunohistochemical method revealed positivity in 80.6% of patients; biochemical measurement yielded 76.2% positive results. The progesterone receptor measured by immunohistochemistry yielded 61.3% positivity versus 55.8% detected by biochemical analysis. Invasive lobular, tubular, and ductal invasive carcinoma with prominent stroma content ("scirrhous carcinoma") rather than ductal invasive carcinoma was more frequently estrogen-receptor positive with immunohistochemistry than with biochemical assay. For progesterone receptor, the same pattern of positivity was seen with immunohistochemical assay. With progesterone receptor determined biochemically, "scirrhous" and lobular carcinoma showed positive results in a lower proportion than invasive ductal and tubular carcinoma. Significant correlations were observed between the estrogen-receptor status, the histologic grade of malignancy, nuclear polymorphism, and the rate of mitosis with both methods (p < 0.001 respectively). Different correlations were found between tumor size, menopausal status and estrogen receptor status with both assays respectively. For the progesterone receptor status, immunohistochemistry yielded significant correlations with the histologic grade of malignancy, nuclear polymorphism, rate of mitosis (p < 0.001 respectively) as well as growth pattern (p < 0.01), while biochemical analysis revealed a correlation with nuclear polymorphism (p < 0.05). The correlation analysis of both components of the immunoreactive score revealed a more significant impact of percentage of positive cells than of staining intensity. CONCLUSIONS: Immunohistochemistry detected a closer correlation between prognostic factors and receptor data than biochemical analysis.

Determination of placental ferritin-positive peripheral lymphocytes in early stages of breast cancer.

"Ferritin-blocked lymphocytes" or placental ferritin (PLF) -positive T cells have repeatedly been described in the circulation of patients with female breast cancer. Since a monoclonal antibody directed against PLF became available, a study was performed to evaluate its usefulness in an easily reproducible system. One hundred patients with controversial or highly suspicious findings on mammography who subsequently underwent operation entered this trial. Sixty-one healthy blood donors served as controls. Patients with early (lymph-node negative) stages of breast cancer (in situ and T1N0 tumors) revealed significantly higher numbers of PLF-positive cells (9.00% +/- 4.5% and 6.21% +/- 3.4%) as compared with controls or patients with benign lumps (p < 0.001). Patients with negative lymph nodes differed significantly from node-positive patients (9.79% versus 2.55%; p < 0.001), whereas no difference as related to menopausal and estrogen-receptor status was observed. In order to define the sensitivity and specificity of this test, we analyzed four different cutoff levels (3%, 4%, 5%, and 6% of PLF-positive T cells). At a level of PLF-positive lymphocyte cells of 4%, 94% of cancer patients with stage T1N0 disease or ductal carcinoma in situ, 5% of patients with benign lumps, and 7% of healthy controls were identified. Furthermore, 88% of all lymph node-negative cancer patients had more than 4% positive cells, compared with only 25% in patients with axillary node involvement. The fact that more than 90% of all patients with in situ carcinomas and patients with stage T1N0 cancer had values above 4% offers promising aspects for this method to be used to complement mammography in the early detection of breast cancer.

[First manifestation of non-Hodgkin's lymphoma in the labia major]. / Die Erstmanifestation eines Non-Hodgkin-Lymphoms im Labium majus.

In this report the case of an extranodal Non-Hodgkin's lymphoma with its manifestation in the external genitalia is described. The necessity of histological examination as well as the need of an cytostatic therapy is shown.

Expression of p43 associated placental isoferritin (PLF) correlates inversely with cell growth in breast cancer cell lines MCF-7 and T47-D.

We have previously demonstrated that the expression of the recently described immunosuppressive antigen p43 in breast cancer patients correlates with early stages of the disease and a low degree of proliferation of the tumors. Attempts were made to evaluate the expression of p43 in two breast cancer cell lines (MCF-7 and T47-D) stimulated to proliferation by 17-beta estradiol and fetal bovine serum (FBS). p43 expression was determined by RIA technique using the new monoclonal antibody CM-H-9, the rate of proliferation was assessed by [3H]thymidine incorporation during 72 hours of incubation. Induction of proliferation by addition of 17-beta estradiol and FBS to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. The level of p43 expression in nonstimulated cells was low in comparison to that in cells cultivated routinely (15% FBS, no estrogen). However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen stimulated proliferation. Our in vitro results confirmed previous clinical observations describing an inverse correlation between p43 synthesis and degree of proliferation and differentiation in breast cancer for the first time. However, the pathologic mechanisms leading to this phenomenon need to be elucidated.

Expression of p43 in breast cancer tissue, correlation with prognostic parameters.

Placental isoferritin (PLF) and its unique superheavy chain p43 have been recently described as being synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue and the degree of differentiation and prognosis, we have determined p43 in the cytosol of 122 breast cancer samples by use of the new monoclonal antibody CM-H-9. The synthesis of p43 showed a significantly negative correlation with tumor size (P = 0.0001), histologic grading (P = 0.0038), nuclear pleomorphism (P = 0.0019), rate of mitosis (P = 0.0002), lymphocytic reaction (P = 0.0001) and a significantly direct correlation with estrogen receptor status (P = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multiple Cox model. Therefore it seems that p43's prognostic impact is linked to the highly significant correlation with features of differentiation although a statistical bias in the Cox model due to the limited number of patients must also be taken into account. On the other hand, the significant correlation of p43 expression with factors for good prognosis was striking and consistent and warrants further research of this tumor product.

Determination of placental ferritin (PLF)-positive lymphocytes in women in early stages of breast cancer.

Previous studies have proved that a certain acidic isoform of ferritin is specifically synthesized by the placenta and breast-cancer tissue. In this context it has been further reported that the determination of this so-called placental isoferritin (PLF) on the surface of a subset of peripheral lymphocytes is highly specific and sensitive for early stage breast cancer. By use of the monoclonal antibody CM-H-9 and flow cytometry, the levels of placental ferritin (PLF)-positive cells were determined in 133 female patients undergoing surgical excision of a controversial or highly suspicious lesion of the breast detected by mammography. In addition, 61 healthy blood donors served as controls. Values of PLF-positive cells in breast cancer patients differed significantly from those found in women with benign diseases and healthy controls (3.87% vs. 1.55% and 2.02, respectively; p less than 0.00001). Analysis of prognostic factors in breast cancer patients (tumor size, lymph-node status, menopausal status, estrogen receptor status, histologic grading and grading subfactors) revealed significantly higher levels of PLF-positive cells in lymph-node-negative patients compared with node-positive patients (p less than 0.00001). Furthermore, levels of PLF-positive cells showed a significantly negative correlation with tumor size and nuclear polymorphism. In 15 patients who underwent a guide-wire-directed surgical biopsy for a non-palpable, mammographically suspect lesion, 4 cases of cancer correlated with high values of PLF-positive lymphocytes while only 1 patient with a benign histologic result exhibited more than 4% positive cells.