E R Fisher

University of Pittsburgh, Pittsburgh, PA, United States

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Publications (259)2141.39 Total impact

  • Bernard Fisher, Carol K Redmond, Edwin R Fisher
    Journal of Clinical Oncology 06/2008; 26(13):2068-71. · 17.88 Impact Factor
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    ABSTRACT: Uncertainties continue to exist concerning the outcomes and management of small (T1a/b N0 M0) invasive breast cancers. A central pathology review was performed of 638 such lesions from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial B-21. Univariate analysis revealed a high risk for ipsilateral breast tumor recurrence with tumors exhibiting a ductal carcinoma in situ component or poor nuclear grade. The converse (protective effect) was found with tumors arising in radial scars, those of tubular histologic type, and those with moderate/marked tumor stroma. The correlations were generally similar for disease-free survival. However, only nuclear grade was found to be independently significant for both of these outcomes. Only lymphatic tumor extension was univariately and multivariately significant for overall survival. The long-term results of follow-up (median, 11.2 years) from the current trial continue to support the need for local breast irradiation and adjuvant therapy in the management of patients with these small cancers.
    Cancer 12/2007; 110(9):1929-36. · 4.90 Impact Factor
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    ABSTRACT: We sought to identify the risk of axillary node involvement in patients with ductal carcinoma in situ (DCIS) and to determine whether axillary node assessment is necessary in these patients. Sentinel node biopsy (SNB) is replacing standard axillary lymph node dissection (ALND) for surgical staging of invasive breast cancer. Its use in patients with DCIS versus local excision (LE), observation, and/or breast irradiation remains in question. We examined the records of 813 patients with localized DCIS and disease-negative margins after LE who were randomly assigned to no further therapy or to breast irradiation in National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-17 and 1799 patients randomized to receive placebo or tamoxifen after LE + radiotherapy in NSABP trial B-24. An ALND was performed in 253 patients in NSABP B-17 and in 162 in NSABP B-24. We found that in NSABP trial B-17, seven patients developed ipsilateral nodal recurrence (INR). Overall INR rate was 0.83/1000 patient-years. In NSABP B-24, overall INR rate was 0.36/1000 patient-years. INR can be considered a surrogate for axillary involvement at the time of DCIS diagnosis. INR in patients with DCIS treated conservatively is extremely rare. Our findings do not support the routine use of SNB in patients with conservatively treated, localized DCIS.
    Annals of Surgical Oncology 09/2007; 14(8):2202-8. · 3.94 Impact Factor
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    ABSTRACT: Central pathology review of ductal carcinoma in situ from 1,456 patients enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-24 was performed to determine predictors for ipsilateral breast tumor recurrences and contralateral breast cancers. Findings after a median follow-up time of 10.5 years revealed ductal comedo necrosis, micropapillary histologic tumor type, and multifocality to be independent high risk factors for ipsilateral breast tumor recurrence. Risk increased for slight comedo necrosis vs absent and for moderate to marked comedo necrosis vs slight. The presence of a micropapillary tumor type and gross tumor size (> or = 1.0 cm) were independently found as risk factors for contralateral breast cancers. Although 47% of ipsilateral and 66% of contralateral events were invasive carcinomas, overall mortality was only 2.3%, a conundrum possibly related to the small size of the latter. The similar predictive role of comedo necrosis in this study and that reported previously from NSABP B-17 (total of 2,079 patients) strongly supports its role as a simple high-risk predictor for ipsilateral breast tumor recurrences.
    American Journal of Clinical Pathology 07/2007; 128(1):86-91. · 3.01 Impact Factor
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    ABSTRACT: In 1972, a prospective, randomized, multi-institutional, cooperative clinical trial was begun to evaluate the efficacy of prolonged 1-phenylalanine mustard (L-PAM) administration following operation in lengthening the disease free interval of patients with primary breast cancer. That protocol using a single agent was the first of a series directed toward evaluating successively more complex chemotherapeutic regimens in an attempt to define subsets of patients which might be responsive to less therapy than others. When it was observed that L-PAM prolonged the disease free interval, particularly of premenopausal patients, findings were reported and a new evaluation comparing L-PAM with L-PAM plus 5-fluorouracil (5-FU) was begun. Upon completion of patient accrual in that protocol, an additional trial comparing L-PAM and 5-FU with L-PAM, 5-FU and Methotrexate was implemented. The present report updates findings from the initial study and presents those from the second. It compares results across the first two protocols as well as between groups within a protocol. While insufficient time has elapsed for determining the ultimate worth of the modalities employed, findings from the second protocol confirm those previously reported indicating that L-PAM lengthens the disease free interval following mastectomy. The combination of L-PAM with 5-FU resulted in a reduction of treatment failure at 12 months which is as good or better than that observed with L-PAM in the first protocol lending further credibility to the earlier findings. While at the end of the first year following mastectomy there was alomst a 50% reduction in treatment failures in patients aged 50 or over (post-menopausal), by 18 months the reduction was 23% and at two years, based on small numbers of patients, only 5%. Examination of results from the first protocol (placebo vs L-PAM) after two years reveals a most highly significant effect of L-PAM in pre-menopausal women with one to three positive nodes. There is an 89% reduction of treatment failures. A similar but less striking effect is noted for those under 50 with ≥four positive nodes. In older patients in both nodal categories, the early observed effect for L-PAM has decreased with time. Inter-protocol comparisons relative to survival are premature. At two years survival in L-PAM patients is 36% greater than in those receiving placebo. It is somewhat better in every subgroup for those receiving L-PAM. Information relative to the effect of these agents on patient toxicity and loco-regional treatment failures is presented. All of the findings stress the urgency for obtaining results on subsets of patients rather than on a population as a whole and they lend support to the thesis that since breast cancer is an eponym to describe a heterogeneous group of tumors residing in a heterogeneous group of women, it is unlikely that uniformly qualitative and quantitative systemic regimens of therapy will be required for every patient.
    Cancer 06/2006; 39(6):2883 - 2903. · 5.20 Impact Factor
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    ABSTRACT: Between 1971 and 1974, 1665 women with primary operable breast cancer were randomized into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial (B-04) conducted to evaluate the effectiveness of several different regimens of surgical and radiation therapy. No systemic therapy was given. Cells from archival paraffin-embedded tumor tissue taken from 398 patients were analyzed for ploidy and S-phase fraction (SPF) using flow cytometry. Characteristics and outcome of patients with satisfactory DNA histograms were comparable to those from whom no satisfactory cytometric studies were available. In patients with diploid tumors (43%), the mean SPF was 3.4% ± 2.3%; in the aneuploid population (57%), the SPF was 7.9% ± 6.3%. Only 29.9% ± 17.3% of cells in aneuploid tumors were aneuploid. Diploid tumors were more likely than aneuploid tumors to be of good nuclear grade (P less than 0.001) and smaller size (P equals 0.03). More tumors with high SPF were of poor nuclear grade than were tumors with low SPF (P equals 0.002). No significant difference in 10-year disease-free survival (P equals 0.3) or survival (P equals 0.1) was found between women with diploid or aneuploid tumors. Patients with low SPF tumors had a 13% better disease-free survival (P equals 0.006) than those with a high SPF and a 14% better survival (P equals 0.007) at 10 years than patients with high SPF tumors. After adjustment for clinical tumor size, the difference in both disease-free survival and survival between patients with high and low SPF tumors was only 10% (P equals 0.04 and 0.08, respectively). Although SPF was found to be of independent prognostic significance for disease-free survival and marginal significance for survival, it did not detect patients with such a good prognosis as to preclude their receiving chemotherapy. The overall survival of patients with low SPF was only 53% at 10 years. These findings and those of others indicate that additional studies are necessary before tumor ploidy and SPF can be used to select patients who should or should not receive systemic therapy.
    Cancer 06/2006; 68(7):1465 - 1475. · 5.20 Impact Factor
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    ABSTRACT: During the 1970s, information obtained from animal tumor models and from patients with a spectrum of solid tumors indicated the worth of a variety of immunostimulating agents. These findings provided a biological and clinical rationale for conducting randomized trials to evaluate the worth of those agents. Consequently, in May 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented a randomized trial to determine whether Corynebacterium parvum (C. parvum, CP) plus chemotherapy would be more effective than chemotherapy alone in prolonging the disease-free survival (DFS) and survival (S) of patients with primary operable breast cancer and positive axillary nodes. The results of that trial through 8 years of follow-up fail to indicate that treatment with CP used in conjunction with 1-phenylalanine mustard (L-PAM) plus 5-fluorouracil (PF) results in a better DFS and S than that observed after chemotherapy alone. Use of the immunomodulator has instead resulted in a poorer, but not statistically significant, outcome. Despite adjustments made to account for any imbalance in distribution of prognostic factors between the two treatment groups and despite considering treatment compliance as a factor, the unfavorable outcome persisted. A high incidence of fever and chills was associated with the administration of CP. The administration of hydrocortisone before each CP treatment reduced the frequency of those and other systemic effects. The failure to demonstrate a benefit from CP is in keeping with the failure of other nonspecific stimulating agents to contribute to the creation of a new paradigm for the treatment of breast cancer.
    Cancer 06/2006; 66(2):220 - 227. · 5.20 Impact Factor
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    Edwin R. Fisher, John Gruhn
    Cancer 01/2006; 10(1):57-62. · 4.90 Impact Factor
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    Edwin R. Fisher, John Gruhn, P SKERRETT
    Cancer 01/2006; 11(3):643-8. · 4.90 Impact Factor
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    ABSTRACT: BACKGROUND The authors attempted to resolve the dilemma posed by the lack of unanimity concerning the optimal immunohistochemical (IHC) method for determining and scoring estrogen receptor (ER) and progesterone receptor (PR).METHODS Sections for IHC were prepared from paraffin embedded tumor samples from 402 patients with lymph node positive breast carcinoma who had biochemical receptor values (obtained with the dextran-coated charcoal [DCC] method) and who were enrolled in a prospective, randomized trial (National Surgical Adjuvant Breast and Bowel Project protocol B-09). IHC receptors were scored independently by two observers according to percent, intensity, and any-or-none algorithms. Results from these evaluations and from two computer-assisted evaluations, DCC, and common pathologic characteristics were analyzed for optimum splits for positive reactions in univariate and multivariate analyses using a tree-structured model. Concordance, sensitivity, and specificity were determined between the DCC method and all other methods.RESULTSInterobserver agreement and concordance between the DCC method and the other methods and among the methods were high. Univariate analyses revealed that a positive ER score obtained with all methods was related significantly to overall survival (OS) at 5 years and at 10 years. Results related to PR scores and disease-free survival and recurrence-free survival were less consistent. In multivariate analysis, it also was found that all methods for scoring ER predicted a better prognosis for OS in patients with an unfavorable lymph node status at 5 years and 10 years. Patients in a favorable lymph node status group were discriminated further by nuclear grade.CONCLUSIONS All IHC methods for scoring ER appeared valid as prognostic indicators of OS in patients with positive lymph nodes. The any-or-none IHC method, by virtue of its simplicity, represents an appropriate choice for practical use. Cancer 2005. © 2004 American Cancer Society.
    Cancer 12/2004; 103(1):164 - 173. · 5.20 Impact Factor
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    ABSTRACT: The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.
    New England Journal of Medicine 12/2004; 351(27):2817-26. · 54.42 Impact Factor
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    ABSTRACT: Findings from the National Surgical Adjuvant Breast and Bowel Project B-14 and B-20 trials showed that tamoxifen benefited women with oestrogen-receptor-positive tumours and negative axillary nodes, and that chemotherapy plus tamoxifen was more effective than tamoxifen alone. We present long-term findings from those trials and relate them to age, menopausal status, and tumour oestrogen-receptor concentrations. We also discuss the extent of progress made in the treatment of such patients. B-14 patients were randomly assigned to placebo (n=1453) or tamoxifen (n=1439); B-20 patients to tamoxifen (n=788) or cyclophosphamide, methotrexate, fluorouracil, and tamoxifen (CMFT, n=789). Primary endpoints were recurrence-free survival and overall survival estimated according to patients' age, menopausal status, and tumour oestrogen-receptor concentration. Smoothed recurrence rates were used to measure patterns of recurrence as a continuous function of age. Compared with placebo, tamoxifen benefited women in B-14 through 15 years, irrespective of age, menopausal status, or tumour oestrogen-receptor concentration (hazard ratio [HR] for recurrence-free survival 0.58, 95% CI 0.50-0.67, p<0.0001; HR for overall survival 0.80, 0.71-0.91, p=0.0008). In B-20, the benefit from CMFT over 12 years was greater than that from tamoxifen alone (HR for recurrence-free survival 0.52, 0.39-0.68, p<0.0001; HR for overall survival 0.78, 0.60-1.01, p=0.063). When CMFT was compared with placebo, there were reductions in treatment failure of about 65% in all age-groups. Much benefit has been achieved in treatment of women with oestrogen-receptor-positive tumours and negative nodes. When planning systemic therapy for such patients of all ages, it should be understood that some have tumours with variable concentrations of oestrogen-receptors, a surrogate for other biomarkers associated with tumour growth and response to treatment. Older women tend to have higher tumour oestrogen-receptor concentrations and are more likely to benefit from tamoxifen than from chemotherapy; in younger women, the converse is true. Consequently, the notion that use of tamoxifen or chemotherapy should be based only on age is too restrictive.
    The Lancet 09/2004; 364(9437):858-68. · 39.21 Impact Factor
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    ABSTRACT: The current report represents a 12-year clinicopathologic update of an earlier 5-year analysis of 180 patients with lobular carcinoma in situ (LCIS) who were treated with local excision and subsequent surveillance only. Nineteen pathologic characteristics of LCIS were assessed as potential predictors of invasive and noninvasive ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR) as well as mortality. Overall, only 26 IBTRs (14.4%) and 14 CBTRs (7.8%) were observed. Nine IBTRs (5.0% of the total cohort) and 10 CBTRs (5.6% of the total cohort) were invasive carcinomas. Eight of 9 IBTRs (88.9%) and 6 of 8 invasive CBTRs (75%) that had histologic sections available for review were of the lobular invasive type. Ninety-six percent of all IBTRs and 100% of invasive IBTRs occurred within the same site as the index LCIS. The numbers of invasive IBTRs were comparable within and after 5 years (5 invasive IBTRs vs. 4 IBTRs). Recurrences of invasive CBTR occurred later than recurrences of invasive IBTR, with 70% of invasive CBTRs recognized after 5 years compared with 44% of invasive IBTRs. It was found that Grade 2-3 LCIS was significantly predictive for invasive IBTR when combined with the number of recurrences of ductal carcinoma in situ (DCIS) alone or with LCIS. Only 2 patients in the cohort (1.1%) succumbed to breast carcinoma; 1 patient had a prior invasive IBTR, and the other patient had an invasive CBTR. The reasons for the lower frequency of invasive recurrences and the higher proportions of the lobular invasive phenotype than noted by others are discussed along with the impact of the findings on the nomenclature, precursor nature, and treatment of LCIS. LCIS is a more indolent form of in situ breast carcinoma than DCIS, with which it shares other features of its natural history, particularly very low mortality rates. There is no compelling reason to surgically treat LCIS other than conservatively. The values of other adjuvant modalities in the management of LCIS are discussed. The authors acknowledge that their findings are based on relatively few events and, even at 12 years, may be regarded as "preliminary". Nonetheless, their findings may reflect the true biologic nature of LCIS.
    Cancer 02/2004; 100(2):238-44. · 4.90 Impact Factor
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    ABSTRACT: Results of the few extant reports concerning the clinical significance of so-called "occult micrometastases" of lymph nodes of patients with Dukes A and B colorectal cancer have been variable. We examined the presumably negative nodes of a larger cohort of such patients who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trials R-01 and C-01 for the influence of what we preferably designate as nodal mini micrometastases on parameters of survival. Mini micrometastases were detected by immunohistochemical staining of the original lymph node sections with anticytokeratin A1/A3 in a total of 241 Dukes A and B patients with rectal and 158 with colonic cancers. Their frequency, as well as that of nuclear and histologic grades, and an estimation of their relationship to relative risks were correlated with overall and recurrence-free survival by univariate and multivariate analyses. Nodal mini micrometastases were detected in 73 of 399 (18.3 percent) patients of this cohort. They failed to exhibit any significant relationship to overall or recurrence-free survival. No association between the assessments of tumor differentiation and mini micrometastases was found. Nuclear and histologic grades also failed to further discriminate overall or recurrence-free survival in patients with A or B stages of colonic or rectal cancers in this cohort. The immunohistochemical demonstration of nodal mini micrometastases failed to discriminate high- and low-risk groups of patients with colorectal cancer who were designated as being node-negative after routine pathologic examination.
    Diseases of the Colon & Rectum 09/2003; 46(8):1021-5; discussion 1025-6. · 3.20 Impact Factor
  • The Breast 03/2003; 12. · 2.58 Impact Factor
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    ABSTRACT: This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of </= 1 cm, by speculation that tamoxifen (TAM) might be as or more effective than radiation therapy (XRT) in reducing the rate of ipsilateral breast tumor recurrence (IBTR) in such women, and by the thesis that both modalities might be more effective than either alone. After lumpectomy, 1,009 women were randomly assigned to TAM (n = 336), XRT and placebo (n = 336), or XRT and TAM (n = 337). Rates of IBTR, distant recurrence, and contralateral breast cancer (CBC) were among the end points for analysis. Cumulative incidence of IBTR and of CBC was computed accounting for competing risks. Results with two-sided P values of.05 or less were statistically significant. XRT and placebo resulted in a 49% lower hazard rate of IBTR than did TAM alone; XRT and TAM resulted in a 63% lower rate than did XRT and placebo. When compared with TAM alone, XRT plus TAM resulted in an 81% reduction in hazard rate of IBTR. Cumulative incidence of IBTR through 8 years was 16.5% with TAM, 9.3% with XRT and placebo, and 2.8% with XRT and TAM. XRT reduced IBTR below the level achieved with TAM alone, regardless of estrogen receptor (ER) status. Distant treatment failures were infrequent and not significantly different among the groups (P =.28). When TAM-treated women were compared with those who received XRT and placebo, there was a significant reduction in CBC (hazard ratio, 0.45; 95% confidence interval, 0.21 to 0.95; P =.039). Survival in the three groups was 93%, 94%, and 93%, respectively (P =.93). In women with tumors </= 1 cm, IBTR occurs with enough frequency after lumpectomy to justify considering XRT, regardless of tumor ER status, and TAM plus XRT when tumors are ER positive.
    Journal of Clinical Oncology 10/2002; 20(20):4141-9. · 17.88 Impact Factor
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    ABSTRACT: In 1976, we initiated a randomized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer. A total of 1851 women for whom follow-up data were available and nodal status was known underwent randomly assigned treatment consisting of total mastectomy, lumpectomy alone, or lumpectomy and breast irradiation. Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained. The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation, as compared with 39.2 percent in the women who underwent lumpectomy without irradiation (P<0.001). No significant differences were observed among the three groups of women with respect to disease-free survival, distant-disease-free survival, or overall survival. The hazard ratio for death among the women who underwent lumpectomy alone, as compared with those who underwent total mastectomy, was 1.05 (95 percent confidence interval, 0.90 to 1.23; P=0.51). The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation, as compared with those who underwent total mastectomy, was 0.97 (95 percent confidence interval, 0.83 to 1.14; P=0.74). Among the lumpectomy-treated women whose surgical specimens had tumor-free margins, the hazard ratio for death among the women who underwent postoperative breast irradiation, as compared with those who did not, was 0.91 (95 percent confidence interval, 0.77 to 1.06; P=0.23). Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer. This decrease was partially offset by an increase in deaths from other causes. Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.
    New England Journal of Medicine 10/2002; 347(16):1233-41. · 54.42 Impact Factor
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    ABSTRACT: Examination was performed on pathologic material from patients enrolled in the National Surgical Adjuvant Breast Project (NSABP) protocol B-18, in which the clinical effects of preoperative (preop) and postoperative (postop) doxorubicin and cyclophosphamide (AC) were compared. Of the total number of 1523 patients, 1234 patients (81%) were in the pathologically evaluable cohort. Six hundred twenty-six patients had been randomized prospectively to receive AC postop and 608 had been randomized to receive AC preop. Preentry diagnosis was made by fine-needle aspiration (FNA) and/or Tru-cut biopsy (TC). AC-induced and other pathologic changes were identified, and their relation to pathologic response and overall survival (OS) and disease-free survival (DFS) was determined. Frequencies of the number of lymph node metastases, their size, stromal reaction, and extracapsular extension (ECE) were compared in the two treatment groups, as was their correlation with OS and DFS. Survival estimates were based on 9 years of follow-up. Approximately 13% of primary breast carcinoma cases exhibited both a clinical complete response (cCR) and a pathologic complete response (absence of invasive tumor [pCR]) to preop AC. An additional 7% of patients exhibited a pCR in the absence of a cCR. A pCR occurred in 38% of those patients determined to have achieved a cCR. Poor nuclear grade of the tumor cells in the pre-entry FNA and/or TC specimens significantly predicted a pCR. Patients with the latter exhibited a better OS and DFS compared with those with a pathologic partial response (presence of sparse invasive tumor [pPR]) or no pathologic response (pNR). Epithelial alterations considered to be induced in tumors by preop AC were comprised of types 1 and 2 giant cells with meganuclei, apocrine metaplasia, and cytoplasmic vacuolation. They had a high degree of specificity (range, 86-99%) but a low sensitivity (range, 7-38%). All were predictive of a pPR and were found to be related adversely to OS and DFS. A fibrous stromal reaction noted in tumors or their putative sites in the preop group was found to have only modest degrees of specificity (63%) and sensitivity (74%). Moderate/marked sclerosis of basement membranes of the ductal and ductular elements of the terminal ductolobular unit (TDLU) was significantly more frequent in nontumor-bearing areas of breasts from patients in the preop treatment group compared with those in the postop treatment group (67% vs. 48%; P < 0.0001). The degrees of change in the TDLU in patients in the postop treatment group were found to be unrelated to age. Lymphatic tumor extension in the primary tumor, as well as a positive lymph node status, were less frequent in the preop treatment group compared with the postop treatment group. The OS and DFS were nearly identical in both treatment groups, being 69% and 55% and 70% and 53% in the preop and postop treatment groups, respectively, at 9 years. A fibrous stromal response to lymph node metastases was found to be significant for DFS but not OS. ECE was similar in both groups (55% vs. 48%; P = 0.12). Only 1% of ECE was found to be related to axillary failure in both treatment arms combined. There was no significant difference with regard to the parameters of survival for patients in the postop treatment group whose lymph nodes contained micrometastases (< 2.0 mm) or mini micrometastases (< 1.0 mm) (the latter detected immunohistochemically with anticytokeratin), and a true-negative lymph node status (not immunohistochemically converted to positive). Conversely, there was no apparent difference with regard to OS in preop treated patients with lymph node micrometastases, mini micrometastases, and macrometastases (P = 0.19). Those with mini micrometastases had a significantly worse OS compared with those with a true-negative lymph node status (P = 0.0007). DFS remained worse for patients in that treatment group with micrometastases and mini micrometastases compared with those with negative lymph nodes, although it was better than that for patients with macrometastases (P = 0.02). Poor nuclear grade of tumor cells in the preentry FNA or TC specimens in the preop group was predictive of a pCR. AC-induced meganuclear giant cells and apocrine changes and nuclear and histologic grades of the primary tumors also were found to be prognostically significant in patients in the preop treatment group, and the latter two variables were found to be significant for those patients in the postop treatment group. No evidence was found to support the need for axillary lymph node radiation for ECE of lymph node metastases. Extended pathologic or immunohistochemical procedures also appear to be unnecessary for the detection of lymph node mini micrometastases, at least when traditional postop chemotherapy is used. The adverse relation between such small metastases and OS and DFS after preop AC appears to be related to the timing of the chemotherapy administration rather than any pathobiologic reasons.
    Cancer 09/2002; 95(4):681-95. · 4.90 Impact Factor
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    ABSTRACT: In women with breast cancer, the role of radical mastectomy, as compared with less extensive surgery, has been a matter of debate. We report 25-year findings of a randomized trial initiated in 1971 to determine whether less extensive surgery with or without radiation therapy was as effective as the Halsted radical mastectomy. A total of 1079 women with clinically negative axillary nodes underwent radical mastectomy, total mastectomy without axillary dissection but with postoperative irradiation, or total mastectomy plus axillary dissection only if their nodes became positive. A total of 586 women with clinically positive axillary nodes either underwent radical mastectomy or underwent total mastectomy without axillary dissection but with postoperative irradiation. Kaplan-Meier and cumulative-incidence estimates of outcome were obtained. No significant differences were observed among the three groups of women with negative nodes or between the two groups of women with positive nodes with respect to disease-free survival, relapse-free survival, distant-disease-free survival, or overall survival. Among women with negative nodes, the hazard ratio for death among those who were treated with total mastectomy and radiation as compared with those who underwent radical mastectomy was 1.08 (95 percent confidence interval, 0.91 to 1.28; P=0.38), and the hazard ratio for death among those who had total mastectomy without radiation as compared with those who underwent radical mastectomy was 1.03 (95 percent confidence interval, 0.87 to 1.23; P=0.72). Among women with positive nodes, the hazard ratio for death among those who underwent total mastectomy and radiation as compared with those who underwent radical mastectomy was 1.06 (95 percent confidence interval, 0.89 to 1.27; P=0.49). The findings validate earlier results showing no advantage from radical mastectomy. Although differences of a few percentage points cannot be excluded, the findings fail to show a significant survival advantage from removing occult positive nodes at the time of initial surgery or from radiation therapy.
    New England Journal of Medicine 09/2002; 347(8):567-75. · 54.42 Impact Factor
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    ABSTRACT: The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted two sequential randomized clinical trials to aid in resolving uncertainty about the treatment of women with small, localized, mammographically detected ductal carcinoma in situ (DCIS). After removal of the tumor and normal breast tissue so that specimen margins were histologically tumor-free (lumpectomy), 818 patients in the B-17 trial were randomly assigned to receive either radiation therapy to the ipsilateral breast or no radiation therapy. B-24, the second study, which involved 1,804 women, tested the hypothesis that, in DCIS patients with or without positive tumor specimen margins, lumpectomy, radiation, and tamoxifen (TAM) would be more effective than lumpectomy, radiation, and placebo in preventing invasive and noninvasive ipsilateral breast tumor recurrences (IBTRs), contralateral breast tumors (CBTs), and tumors at metastatic sites. The findings in this report continue to demonstrate through 12 years of follow-up that radiation after lumpectomy reduces the incidence rate of all IBTRs by 58%. They also demonstrate that the administration of TAM after lumpectomy and radiation therapy results in a significant decrease in the rate of all breast cancer events, particularly in invasive cancer. The findings from the B-17 and B-24 studies are related to those from the NSABP prevention (P-1) trial, which demonstrated a 50% reduction in the risk of invasive cancer in women with a history of atypical ductal hyperplasia (ADH) or lobular carcinoma in situ (LCIS) and a reduction in the incidence of both DCIS and LCIS in women without a history of those tumors. The B-17 findings demonstrated that patients treated with lumpectomy alone were at greater risk for invasive cancer than were women in P-1 who had a history of ADH or LCIS and who received no radiation therapy or TAM. Although women who received radiation benefited from that therapy, they remained at higher risk for invasive cancer than women in P-1 who had a history of LCIS and who received placebo or TAM. Thus, if it is accepted from the P-1 findings that women at increased risk for invasive cancer are candidates for an intervention such as TAM, then it would seem that women with a history of DCIS should also be considered for such therapy in addition to radiation therapy. That statement does not imply that, as a result of the findings presented here, all DCIS patients should receive radiation and TAM. It does suggest, however, that, in the treatment of DCIS, the appropriate use of current and better therapeutic agents that become available could diminish the significance of breast cancer as a public health problem.
    Seminars in Oncology 09/2001; 28(4):400-18. · 3.94 Impact Factor

Publication Stats

22k Citations
2,141.39 Total Impact Points


  • 1958–2008
    • University of Pittsburgh
      • • Department of Surgery
      • • Department of Radiation Oncology
      • • School of Medicine
      • • Department of Medicine
      • • Division of Pathology at UPMC Shadyside Hospital
      • • Department of Pathology
      Pittsburgh, PA, United States
  • 1998–1999
    • American University of Health Sciences
      United States
  • 1972–1999
    • Shadyside Hospital
      Shadyside, Ohio, United States
    • Magee-Womens Hospital
      Pittsburgh, Pennsylvania, United States
  • 1981
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States