Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer.

PURPOSE: To evaluate the feasibility of allogeneic peripheral-blood progenitor-cell (PBPC) transplantation and to assess graft-versus-tumor effects in patients with metastatic breast cancer. PATIENTS AND METHODS: Ten patients with metastatic breast cancer that involved the liver or bone marrow were treated with high-dose chemotherapy and allogeneic PBPC transplantation. The median age was 42 years (range, 29 to 55). The median number of metastatic sites was three (range, one to five). The conditioning regimen was cyclophosphamide (6,000 mg/m2), carmustine (BCNU; 450 mg/m2), and thiotepa (720 mg/m2) (CBT regimen). Patients received graft-versus-host disease (GVHD) prophylaxis using cyclosporine- or tacrolimus-based regimens. RESULTS: All patients had engraftment and hematologic recovery. Three patients developed grade > or = 2 acute GVHD and four patients had chronic GVHD. After transplantation, one patient was in complete remission (CR), five achieved a partial remission (PR), and four had stable disease (SD). In two patients, metastatic liver lesions regressed in association with skin GVHD after withdrawal of immunosuppressive therapies. The median follow-up time was 408 days (range, 53 to 605). The median progression-free survival duration was 238 days (range, 53 to 510). CONCLUSION: We conclude that allogeneic PBPC transplantation is a feasible procedure for patients with poor-risk metastatic breast cancer. The regression of tumor associated with GVHD provides suggestive clinical evidence that graft-versus-tumor effects may occur against breast cancer. Compared with autologous transplantation, allogeneic PBPC transplantation is associated with the additional risks of GVHD and related infections. Allogeneic transplantation should only be performed in the context of clinical trials and its ultimate role requires demonstration of improved progression-free survival.

Hodgkin's disease: correlation of clinical characteristics with probabilities for negative lymphangiogram vs. negative laparotomy findings in patients with Stage I supradiaphragmatic presentations vs. those in patients with Stage II.

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.

The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis.

The effect of hematopoietic growth factors on neutrophil recovery after allogeneic transplantation is well-recognized. Recent laboratory studies demonstrated that these cytokines may also modify T-cell and dendritic cell function, but whether the effect is strong enough to alter the risk of GVHD is unclear. We performed a meta-analysis to determine the effect of G-CSF or GM-CSF on the risk of nonhematopoietic outcomes after allogeneic transplantation. A search of the literature from 1986 to present yielded 18 publications in which data were provided for cohorts receiving growth factor vs either placebo or no therapy. These included nine prospective randomized studies, eight retrospective cohort studies, and one case-control study comprising a total of 1198 patients. The publication types were heterogeneous with regard to demographic and treatment characteristics, although within publications, comparative groups were generally balanced. The pooled risk ratio estimates with use of growth factor was 1.08 (95% CI 0.87-1.33, P=0.48) for grades 2-4 acute GVHD, 1.22 (95% CI 0.80-1.86, P=0.99) for grades 3-4 acute GVHD, and 1.02 (95% CI 0.82-1.26, P=0.87) for chronic GVHD. This analysis did not detect a significant change in the risk of acute or chronic GVHD after allogeneic hematopoietic stem cell transplantation when hematopoietic growth factors were used to shorten the initial period of neutropenia.

Combination therapy with aerosolized ribavirin and intravenous immunoglobulin for respiratory syncytial virus disease in adult bone marrow transplant recipients.

Respiratory syncytial virus (RSV) infections in adult BMT recipients are frequently complicated by fatal pneumonias. Therapy of RSV pneumonia with aerosolized ribavirin alone has been reported to be associated with a 70% mortality rate. Because immune globulin therapy has been reported to be beneficial, we conducted a prospective trial of combination therapy with aerosolized ribavirin and intravenous immunoglobulin (IVIG). Aerosolized ribavirin was administered at 20 mg/ml for 18 h a day and IVIG was administered at 500 mg/kg every other day for the length of ribavirin therapy. Four lots of IVIG were chosen with RSV microneutralization Ab titers of 1:2048 to 1:8102. Between 8 January and 3 March 1993, during a community outbreak, 19 (45%) of 42 hospitalized adult BMT recipients with an acute respiratory illness were documented to have RSV disease. Two-thirds of these infections were hospital-acquired. All 19 patients presented with signs and symptoms of an upper respiratory tract illness. Sixteen patients developed pneumonia. The mortality was 22% in nine patients with pneumonia in whom therapy was initiated prior to the onset of profound respiratory failure. In contrast, the mortality was 100% in three patients with pneumonia in whom therapy was initiated within 24 h of respiratory failure requiring mechanical ventilation and in four untreated patients. We conclude that RSV may cause devastating outbreaks of severe pneumonia among hospitalized adult BMT recipients. Early diagnosis and combination therapy with ribavirin and IVIG was associated with a favorable outcome.

The correlation of axillary ultrasonography with histologic breast cancer downstaging after induction chemotherapy.

BACKGROUND: The goal of this study was to examine the role of ultrasonography in detecting axillary lymph node metastases in stage II breast cancer patients after induction chemotherapy (IC). METHODS: Of 172 consecutive patients with T1-3, N0-1, M0 breast cancer registered in a prospective IC trial, a subset of 130 evaluable patients were chosen, with (1) both physical and ultrasonographic examinations of the axilla before and after IC; (2) exactly four cycles of IC; (3) no presurgical radiation therapy; and (4) an axillary lymph node dissection. RESULTS: Before IC, 32 patients (25%) were negative for axillary involvement by both physical and ultrasonographic examinations. After IC, this number increased to 64 (49%). Of these, 31 (48%) were positive by pathology examination. In most cases, however, the residual tumor was minimal. CONCLUSIONS: Stage II breast cancer patients who were or became node negative by both ultrasonographic and physical examinations after IC had a 48% incidence of nodal metastases. Because the residual tumor was minimal, irradiation may be sufficient for adequate local control of the axilla.

Impact of multicentricity on clinical outcome in patients with T1-2, N0-1, M0 breast cancer.

BACKGROUND: The objective was to determine the impact of multicentric breast cancer on recurrence and survival and to evaluate the current tumor, node, metastasis staging system recommendations for multicentricity in the breast. METHODS: This study included 284 nonpregnant patients with T1-2, N0-1, M0 breast cancer, without previous cancer, who were treated by modified radical mastectomy followed by doxorubicin-based adjuvant chemotherapy. Clinical and pathological data were collected retrospectively and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. RESULTS: The median follow-up time was 8 years (range, 0.3-24.0), and the median age was 47 years (range, 23-76). The median clinical size of the index tumor was 2.5 cm. In 17% of patients, the clinical nodal status was N1. In 84% of patients, pathology of the index lesion was invasive ductal +/- in situ. Multicentric breast cancer was detected in 60 patients (21%): 30 patients with two lesions, 13 patients with three lesions, and 17 patients with four or more lesions. Locoregional recurrence, contralateral breast cancer, distant metastasis, and survival (disease-specific and disease-free) were similar in both groups of multicentric versus unicentric breast tumors. There was a significant difference between groups in estrogen receptor and axillary lymph node positivity, but these did not contribute significantly to outcome on multivariate analysis. CONCLUSIONS: Multicentricity does not increase the risk of poor outcomes in patients with early-stage breast cancer. This supports the current recommendations of the tumor, node, metastasis staging system that tumor size should be based on the diameter of the largest lesion in patients with multicentric breast cancer.

Feasibility of breast preservation in the treatment of occult primary carcinoma presenting with axillary metastases.

BACKGROUND: The objective of the study was to compare the treatment outcomes in patients with occult primary carcinoma with axillary lymph node metastasis who were treated with mastectomy or with intent to preserve the breast. METHODS: From 1951 to 1998, 479 female patients were registered with axillary lymph node metastasis from an unknown primary. After clinical workup, including mammography, 45 patients retained this diagnosis and received treatment for T0 N1-2 M0 carcinoma of the breast. Clinical and pathological data were collected retrospectively, and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. Median follow-up time was 7 years. RESULTS: Median age was 54 years (range, 32-79). Clinical nodal status was N1 in 71% and N2 in 29% of the patients. Surgical treatment was mastectomy in 29% and an intent to preserve the breast in 71% of the patients. Locoregional radiotherapy was used in 71% and systemic chemoendocrine therapy was used in 73% of the patients. Of the 13 mastectomy patients, only one had a primary tumor discovered in the specimen. Two patients (4%) were ultimately diagnosed with lung cancer and neuroendocrine tumor. No significant difference was detected between mastectomy and breast preservation in locoregional recurrence (15% versus 13%), distant metastases (31% versus 22%), or 5-year survival (75% vs. 79%). Regardless of surgical therapy, the most important determinant of survival was the number of positive nodes. Five-year overall survival was 87% with 1-3 positive nodes compared with 42% with > or =4 positive nodes (P < .0001). CONCLUSIONS: Occult primary carcinoma with axillary metastases can be treated with preservation of the breast without a negative impact on local control or survival.

Breast conservation therapy as a treatment option for the elderly. The M. D. Anderson experience.

BACKGROUND: Although almost half of all incidents of breast carcinoma occur in women age > or = 65 years, not enough is known about appropriate care for patients in this age group. The objective of the current study was to evaluate the role of breast conservation therapy in the management of breast carcinoma in women age > or = 65 years. METHODS: From 1970 to 1994, 1325 patients with carcinoma of the breast were treated with breast conservation therapy (segmental mastectomy and radiation therapy with or without axillary lymph node dissection) at The University of Texas M. D. Anderson Cancer Center. From this patient group, the authors identified 184 elderly women (> or = 65 years) with Stage 0-III disease at the time of diagnosis. RESULTS: The median patient age was 70 years (range, 65-88 years). The distribution of disease by stage among the women was Stage 0 disease in 12 patients (7%), Stage I disease in 107 patients (58%), Stage II disease in 63 patients (34%), and Stage III disease in 2 patients (1%). Comorbid conditions that may have influenced treatment planning were reported in 91 patients (50%). An axillary lymph node dissection was performed in 135 patients (73%), with positive axillary lymph nodes found in 30 patients (22%). Adjuvant chemotherapy was given to 10 patients (5%), and tamoxifen therapy was given to 63 patients (34%). Complications from treatment were reported in 24 patients (13%). With a median follow-up of 7.3 years (range, 0.25-23.5 years), 9 patients developed locoregional disease recurrence (5%), 10 patients developed contralateral breast carcinoma (5%), and 21 patients developed distant metastasis (11%). At last follow-up, 113 patients (61%) were alive, 15 patients (8%) were dead of disease, and 56 patients (30%) were dead of other causes. The 5-year and 10-year disease specific survival rates were 96% and 91%, respectively. CONCLUSIONS: Breast conservation therapy with segmental mastectomy and postoperative radiation therapy with or without axillary lymph node dissection provides excellent local control and disease free survival in elderly women with breast carcinoma. This treatment should be considered as the standard of care for elderly patients without severe comorbid disease.

The feasibility of minimally invasive surgery for stage IIA, IIB, and IIIA breast carcinoma patients after tumor downstaging with induction chemotherapy.

BACKGROUND: Induction chemotherapy (IC) has become the standard of care for locally advanced breast carcinoma, frequently downstaging both the primary tumor and the axilla, and making patients eligible for less invasive surgical procedures. The usefulness of IC in earlier stage operable breast carcinoma is now being considered. METHODS: This study involved a subset of 129 patients from a series of 174 with T2-3, N0-1, M0 or T1, N1, M0 breast carcinoma (Stage IIA, IIB, or IIIA ) who were registered in a prospective IC trial using paclitaxel or a combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC). The subset included patients who had received no preoperative radiation therapy but had completed 3-5 cycles of induction chemotherapy and had undergone a Level I-II axillary lymph node dissection. The objective was to evaluate the effectiveness of induction chemotherapy with paclitaxel or FAC in downstaging the primary tumor and axillary metastases in these early stage breast carcinoma patients. RESULTS: The median initial tumor size was 4 cm (range, 0.6-10.0); after IC, tumor size was downstaged to 1.6 cm (range, 0.0-7.0) (P < 0.0001). Clinical response to IC was complete in 24% of patients and partial in 36%. Primary tumor shrinkage was similar with paclitaxel and FAC. Among patients clinically classified as N1, 34% became histologically negative and 38% had only 1-3 positive lymph nodes after induction chemotherapy. CONCLUSIONS: IC with paclitaxel or FAC resulted in effective downstaging of primary tumors and axillary metastases in patients with Stage IIA, IIB, and IIIA breast carcinoma. However, a significant proportion of patients still had residual but low volume microscopic disease; such disease status may allow minimally invasive surgical approaches to locoregional therapy.

Influenza among hospitalized adults with leukemia.

Influenza is one of the most important respiratory diseases of mankind, yet scant data exist concerning the frequency and clinical course of influenza in severely immunocompromised adults. From October 1993 to September 1994, we cultured the respiratory secretions of all adults with leukemia who were hospitalized with an acute respiratory illness at The University of Texas M.D. Anderson Cancer Center in Houston. During a 9-week period from 29 November 1993 to 29 January 1994, influenza virus type A (H3N2) was isolated from 15 (33%) of these 45 hospitalized adults. Twelve (80%) of the cases of influenza were associated with pneumonia, and four patients (33%) with pneumonia died. Patients who died tended to have received chemotherapy more recently and to be more myelosuppressed. Autopsy examination in two cases revealed histopathologic changes consistent with viral pneumonia. During community outbreaks, influenza is a frequent cause of serious respiratory disease in hospitalized adults with leukemia. Effective prophylactic and therapeutic regimens need to be defined for immunocompromised patients.

Respiratory disease due to parainfluenza virus in adult bone marrow transplant recipients.

We reviewed the frequency and clinical course of parainfluenza virus (PIV) infections in 1,173 adult bone marrow transplant (BMT) recipients cared for at The University of Texas M.D. Anderson Cancer Center (Houston). Between January 1991 and September 1994, PIV was isolated from the respiratory secretions of 61 (5.2%) of these patients. Thirty-four (56%) of the 61 patients had uncomplicated upper respiratory tract illnesses and survived. The remaining 27 patients (44%) developed pneumonia, and the associated mortality was 37% (10 of 27 patients). Twenty-three (85%) of the patients with pneumonia had had preceding upper respiratory illnesses. Of the 10 patients who died, nine died within 100 days after transplantation. Histopathologic examination of lung tissue from seven patients revealed intracytoplasmic viral inclusions in six, a finding consistent with invasive PIV pneumonia, and viral changes in the seventh patient. Seven of the 10 patients who died had other serious concurrent infections. Of 42 patients who developed PIV infection early after transplantation (i.e., < 100 days), the frequency of pneumonia was higher among the 18 allogeneic BMT recipients (61%) than among the 24 autologous BMT recipients (42%), and the associated mortality was also higher (55% vs. 30%, respectively). PIVs are an important cause of life-threatening pneumonia in adult BMT recipients, particularly patients who have recently undergone allogeneic bone marrow transplantation.

A case-control study of unilateral and bilateral breast carcinoma patients.

BACKGROUND: Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The clinical significance of bilateral breast carcinoma has not been fully defined, and the subset of patients who may benefit from medical or surgical risk-reduction intervention has not yet been characterized. The purpose of this study was to evaluate risk factors and outcomes for bilateral breast carcinoma. METHODS: A subject group of 70 bilateral breast carcinoma patients (62% metachronous) was matched by age and survival interval with a control group of 70 unilateral breast carcinoma patients. Median follow-up was 103 months. RESULTS: Eighty-two percent of the unilateral patients and 80% of the bilateral patients had Stage I or II disease at diagnosis. Median age at presentation was 53 years. In the bilateral group, the contralateral cancer was diagnosed at the same or earlier stage than the first cancer in 87% of cases. Bilateral patients were significantly more likely to have multicentric disease and to have a positive family history for breast carcinoma compared with the unilateral group. There were no significant differences regarding history of exogenous hormone exposure, lobular histology, hormone-receptor status, or HER-2/neu expression. Five-year disease-free survival was 94% for the unilateral breast carcinoma patients and 91% for the bilateral breast carcinoma patients (P = 0.16). CONCLUSIONS: Survival for patients with bilateral breast carcinoma is similar to that of patients with unilateral disease; however, prophylactic risk-reduction intervention for the contralateral breast should be considered in patients who have multicentric unilateral disease or a positive family history for breast carcinoma.

High CD34 cell doses do not worsen regimen-related toxicity or early mortality after autologous blood stem cell transplantation for breast cancer.

BACKGROUND: Some transplant-related complications, such as the engraftment syndrome, are thought to be mediated by cytokines released during expansion of hematopoietic progenitors at the time of neutrophil recovery. Since there is an inverse correlation between CD34(+) cell dose and time to neutrophil recovery, we sought to determine if peritransplant toxicity and early mortality were adversely affected by high CD34(+) cell doses. METHODS: The study group included 186 women with breast cancer who received high-dose cyclophosphamide, carmustine, thiotepa and an autologous PBSC transplant. The median CD34(+) cell dose was 5.9 x 10(6)/kg (1.0-154.7 x 10(6)/kg). Patients were categorized by CD34(+) cell dose (1.0-3.5, 3.6-5.9, 6.0-19.9, and 20.0-154.7 x 10(6)/kg) for assessment of outcomes. RESULTS: Grades 2-4 mucositis occurred in 49%, cardiac toxicity in 7%, pulmonary toxicity in 5%, cystitis in 4%, diarrhea in 3%, renal toxicity in 1%, and central nervous system toxicity in 1%. A Grade 2-4 regimen-related toxicity occurred in 109 patients (59%) and Grade 3-4 in eight patients (4%). Overall survival was 100% at Day 30, 96% at Day 90, and 89% at 1 year. Treatment-related mortality was 3.8%. In multivariate analyses that included prior chemotherapy, disease status, visceral metastases, prior chest radiation and age, CD34(+) cell dose group was not an independent risk factor for Grade 2-4 mucositis, Grade 2-4 maximum toxicity, Grade > or =3 cumulative toxicity, 90 day survival or 1 year survival. DISCUSSION: We conclude that CD34(+) cell doses >20 x 10(6)/kg do not affect transplant outcome in a negative or positive fashion.

Prognostic implications of pathological lymph node status after preoperative chemotherapy for operable T3N0M0 breast cancer.

BACKGROUND: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo. METHODS: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years. RESULTS: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P = .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P = .01) and disease-specific survival (P = .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4-9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4-9 positive nodes (17 vs. 48%, P = .04). CONCLUSIONS: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.

Ductal carcinoma-in-situ: long-term results of breast-conserving therapy.

BACKGROUND: The role of breast-conserving therapy (BCT) in the management of ductal carcinoma-in-situ (DCIS) is controversial because of reported high recurrence rates. We reviewed our experience to determine whether the rate and pattern of locoregional recurrence after BCT were similar in patients with DCIS and patients with early-stage (T1) invasive breast tumors and whether local recurrence affected survival. METHODS: Between 1973 and 1994, 87 patients with DCIS alone, 22 patients with DCIS with microinvasion (DCIS-M), and 646 patients with invasive breast cancer 2 cm or smaller in diameter were treated with BCT (wide local excision with radiotherapy) at The University of Texas M. D. Anderson Cancer Center. Survival was calculated by the Kaplan-Meier method. The median follow-up times were 11 years for patients with DCIS alone, 12 years for patients with DCIS-M, and 8 years for patients with invasive breast cancer. RESULTS: Eleven (13%) of 87 patients with DCIS and 5 (23%) of 22 patients with DCIS-M had developed locoregional recurrences at follow-up. Two patients with DCIS with locoregional recurrence died of breast cancer. Of the 646 patients with invasive breast cancer, 56 (9%) had a locoregional recurrence, and 16 (2%) died of breast cancer. The median time to locoregional recurrence was significantly longer in patients with DCIS or DCIS-M (9-10 years) than patients with invasive tumors (5 years). CONCLUSIONS: DCIS is a favorable disease with an excellent long-term survival. The locoregional recurrence rate in patients with DCIS treated with BCT is similar to that in patients with early-stage invasive breast cancer treated with BCT, but time to locoregional recurrence is significantly longer in patients with DCIS. In patients with DCIS treated with BCT, intense surveillance for locoregional recurrence needs to be maintained for the patient's lifetime.

Primary tumor response to induction chemotherapy as a predictor of histological status of axillary nodes in operable breast cancer patients.

BACKGROUND: Routine use of axillary lymph node dissection is being questioned, especially in clinically NO patients. The goal of this study was to determine whether primary tumor response to induction chemotherapy (IC) can predict the histological volume of residual axillary disease in patients who were candidates for breast conservation surgery after IC. METHODS: Forty-seven patients with stage II or IIIA breast cancer who received breast conservation surgery were selected from a population of patients randomized to receive four cycles of IC. Largest clinical tumor size before and after IC was determined by physical examination, mammography, and breast ultrasound. Clinical nodal status was determined by physical examination and axillary ultrasound and compared with histological findings. RESULTS: In patients with at least 50% reduction in primary tumor size after IC, 12 of 14 (86%) NO patients and 11 of 17 (65%) N1 patients were histologically negative. In patients with a less than 50% reduction, 0 of 3 NO patients and 2 of 13 (15%) N1 patients were histologically negative. CONCLUSIONS: There is significantly less axillary disease in responders than in nonresponders after IC. For NO responders, axillary irradiation may be an acceptable alternative to axillary lymph node dissection, and could easily be incorporated into the postsurgical radiotherapy that is standard protocol for breast conservation therapy. The more aggressive disease in nonresponders is best treated by axillary lymph node dissection, pending further study.