Estrogen replacement therapy after breast cancer: a 12-year follow-up.

BACKGROUND: In the United States, estrogen replacement therapy (ERT) is discouraged in breast cancer survivors because of concerns that hormones may reactivate the disease. Because ERT can improve quality of life and decrease morbidity from osteoporosis and cardiovascular disease, however, this policy is increasingly being challenged. METHODS: From February to August 1995, 607 breast cancer survivors were interviewed concerning ERT usage. Sixty-four patients indicated they received some form of ERT after their breast cancer diagnosis. Medical records for these patients were analyzed for disease stage, surgical treatment, adjuvant treatment, estrogen and progesterone receptor status, date of initiation of ERT, type of ERT, recurrence, and final outcome. Patients receiving ERT were followed prospectively. RESULTS: Eight patients were excluded because they had used only vaginal cream ERT. The remaining 56 received ERT as conjugated estrogens, an estradiol patch, estropipate, or birth control pills. The median follow-up from diagnosis was 12.8 years (range, 4.7-38.9 years). The median time on ERT since diagnosis was 6.4 years (range, 1.0-20.9 years); 38% of the patients initiated ERT within 2 years of diagnosis. Estrogen receptors were positive in 28 (74%) of the 38 cases with available information. Pathological disease stage at time of diagnosis and treatment was 0 in 15 cases (27%), I in 27 (48%), and II in 14 (25%). Twenty-six patients (47%) received adjuvant chemotherapy or hormonal therapy. One local recurrence and one contralateral breast cancer occurred during the follow-up period (13.5 and 9.6 years, respectively), with no regional or distant recurrences, for a 15-year actuarial disease-free survival rate of 92.5%. There were no breast cancer deaths. CONCLUSIONS: Use of ERT in a cohort of breast cancer survivors with tumors of generally good prognosis was not associated with increased breast cancer events compared with non-ERT users, even over a long follow-up period.

Sentinel lymph node biopsy, an alternative to elective axillary dissection for breast cancer.

BACKGROUND: Axillary metastases remain an important prognostic indicator in breast cancer. Axillary lymphadenectomy (ALND) carries significant morbidity and is unnecessary in most patients with early breast cancer; thus, sentinel lymph node (SLN) biopsy has been advocated for axillary staging. We studied the SLN identification rate and its accuracy in predicting axillary metastases. METHODS: One hundred nineteen women with breast carcinoma underwent SLN and ALND. Lymphoscintigraphy was performed using Technetium99 sulfur colloid supplemented by Isosulfan blue dye. Hematoxylin/eosin-stained lymph node sections were examined by light microscopy. RESULTS: The SLN identification rate was 81%. One SLN was negative (1%) in a patient with axillary disease. SLN histology correctly predicted the absence of axillary disease in 98.6%. Sensitivity, specificity, and positive and negative predictive values were 96%, 100%, 100%, and 99%, respectively. CONCLUSIONS: Sentinel lymph node biopsy accurately predicts total axillary status and is valuable in the surgical staging of breast cancer.

Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging.

BACKGROUND: The implementation of new treatment protocols for locally advanced breast cancer is currently limited by inaccurate evaluation of response to neoadjuvant chemotherapy. A recently developed dedicated breast magnetic resonance imaging (MRI) method (RODEO MRI) was evaluated as a tool for determining tumor response and extent of residual disease after neoadjuvant chemotherapy. METHODS: Thirty-nine patients with Stage II, III, or IV breast carcinoma were prospectively evaluated prior to and following neoadjuvant chemotherapy by MRI, physical examination, and mammography. Assessment of response determined by the three methods was compared. In addition, detailed pathologic correlation of residual disease was determined by serial sectioning of 31 mastectomy specimens from 30 patients. Nine patients had breast conservation, and were included in the response evaluation only. Estimates of tumor response were made by both surgical and medical oncologists. Independent interpretations of MRI studies without knowledge of clinical response were made by three radiologists. RESULTS: The surgical oncologists assessed complete response (CR), partial response (PR), and no response (NR) in 11, 22, and 7 cases, respectively. The medical oncologists assessed CR, PR, and NR in 12, 21, and 7 cases, respectively. The surgical and medical oncologists' clinical assessment of response agreed with the results of MRI in 52% and 55% of cases, respectively, and with each other in 30 of 40 cases (75%). Mammography correlated with MRI response in only 52% of cases. However, MRI accurately predicted the pathologic determination of residual disease in 30 of 31 cases (97%). There was no disagreement in the assessments of residual disease or response among the three radiologists. CONCLUSIONS: RODEO breast MRI accurately estimates residual disease after induction chemotherapy. It assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination or mammography. The information obtained from this MRI technique may be used as an objective tool during clinical trials, and to select patients better for breast conservation after neoadjuvant chemotherapy for locally advanced disease.

Effect of major dietary modifications on immune system in patients with breast cancer: a pilot study.

A pilot study was conducted to evaluate the effect of diet on immune function in nine premenopausal, post-therapy patients with breast cancer. The patients were instructed on following the American Cancer Society dietary guidelines and were told to do so from day 0 to day 28. These guidelines recommend a high-fiber, low-fat diet. On day 29, the patients continued the diet but included fish high in omega-3 fatty acids until day 56. Twenty-four-hour urine and blood samples, and 3-day diet records were obtained on days 0, 28, and 56. The following parameters were monitored: lymphocyte subsets, T-cell function (proliferation and cytolytic response), and urinary prostaglandin E2 (PGE2). Results throughout the study suggested a benefit from decreasing dietary fat intake, and increasing fish intake. Helper T-cell (CD4) percentage increased from day 0 to days 28 and 56 (P = 0.048). Cytotoxic/suppressor T-cell (CD8) percentage decreased from day 0 to days 28 and 56 (P = 0.002). The CD4/CD8 cell ratio increased by days 28 and 56 (P = 0.0004). The proliferation of CD4 cells increased from day 0 to days 28 and 56 (P = 0.005). Significant changes were not found in the cytolytic activity of T cells, natural killer cells, total T and B cells, or urinary prostaglandin E2. Results suggest that patients with breast cancer may benefit from following American Cancer Society dietary guidelines and consuming cold-water ocean fish.

Stereotactic breast biopsy as an alternative to open excisional biopsy.

BACKGROUND: Health care cost continues to play a dominant role in our society. Technological advances are expensive, with the possible exception of stereotactic breast biopsy. We must learn other alternatives that give the same diagnostic accuracy at lower cost. The intention of this study was to find other acceptable alternatives to open excisional breast biopsies. METHODS: Patients were referred to Baylor University Medical Center between May 1990 and June 1992 for stereotactic breast biopsy of nonpalpable mammographic abnormalities. Before stereotactic biopsy, lesions were categorized into low or high suspicion for malignancy based on screening mammography. Slides were reviewed by a pathologist and the histological diagnosis was compared with mammographic characterization. Benign histology confirming the low-suspicion mammographic abnormality demonstrated mammographic and histologic correlation. Mammographic follow-up was recommended. RESULTS: Two hundred twenty-five women underwent 250 stereotactic breast biopsies. Malignancy was diagnosed in 47 patients; the remaining 203 lesions were benign on pathological examination and are being followed regularly. Seventy-eight percent of the lesions were characterized as low suspicion for malignancy, and 22% were characterized as high suspicion. The average cost savings per lesion using stereotactic biopsy was $1,629. CONCLUSION: Stereotactic breast biopsy is an acceptable, less expensive alternative to open excisional biopsy for diagnosing nonpalpable mammographic findings.

New horizons in the diagnosis and treatment of breast cancer using magnetic resonance imaging.

A new nuclear magnetic resonance imaging (MRI) technique, Rotating Delivery of Excitation Off-resonance (RODEO), has been developed to assist surgeons in the diagnosis and treatment of breast cancer. A nonrandomized, prospective study of 100 patients with a high suspicion of breast cancer was conducted; these patients were examined by RODEO and conventional breast imaging, including mammography. Forty-one breasts were removed by mastectomy; each pathologic specimen was examined by sectional analysis. This study was undertaken to determine the extent that RODEO can aid in detecting breast tumors (including multicentric disease) and in evaluating candidates for conservative breast surgery. RODEO detected 85 pathologically confirmed lesions, 64 of which proved to be malignant. RODEO had a sensitivity of 95%, compared with a sensitivity of 58% for conventional imaging. More study is needed to determine distinguishing MRI characteristics that are suspicious for malignancy. RODEO may be used clinically to assess multicentricity and response to chemotherapy.

Cancer in the augmented breast. Diagnosis and prognosis.

BACKGROUND: The stage of breast cancer at diagnosis in women who have undergone augmentation mammoplasty has been examined with conflicting results. Additional evaluation of this population is needed. METHODS: A retrospective review of a large cancer center's breast cancer registry for a 116-month period was performed. Comparisons of patient age, method of detection, and pathologic stage of disease at presentation were performed for 33 patients with augmented breasts and 1735 patients with nonaugmented breasts who were treated. RESULTS: Twenty-four percent of the patients with augmented breasts and 42% of those with nonaugmented breasts had mammographically detected cancers (P = NS). The incidence of ductal carcinoma in situ in the two groups was similar (18% versus 15%). Sizes of the mammographically detected tumors in the two groups were comparable; however, palpable tumors in the augmented group were significantly smaller than were those in the nonaugmented group. Overall, a significant difference in axillary lymph node involvement was detected, with 19% of the augmented group and 41% of the nonaugmented group having positive lymph nodes. In patients with palpable tumors, axillary lymph node involvement also was significantly different, with 22% of the patients with augmented breasts and 58% of those with nonaugmented breasts having axillary lymph node metastases. In the mammographically detected tumors, there was no significant difference in axillary lymph node metastases between the patients with augmented (13%) and those with nonaugmented (15%) breasts. CONCLUSIONS: Early detection of breast cancer is possible in the patient who has undergone augumentation mammoplasty. Mammography was successful in detecting occult lesions, and palpation detected smaller tumors. In this cohort, there was no evidence to suggest that the patients with augmented breasts had more advanced disease at presentation.

Clinical recognition and management of depression in node negative breast cancer patients treated with tamoxifen.

Depression is not an uncommon complaint of women with breast cancer and is usually assumed to be related to the cancer diagnosis itself or its treatment. As part of a prospective clinical trial of adjuvant therapy of node negative breast cancer, 301 patients treated and assessed by one oncologist (SEJ) were serially questioned for symptoms of depression in the first 6-12 months after completing initial treatment (surgery, radiation therapy, and/or chemotherapy). Two hundred and fifty-seven patients were evaluable for assessment of depression; 155 were receiving tamoxifen and 102 were not. Twenty-six patients had symptoms of depression including 23 (15%) treated with tamoxifen compared to 3 (3%) in the group not placed on tamoxifen (p < 0.005). Of the 23 patients with depression in the tamoxifen group, symptoms were temporally related to the initiation of therapy and occurred generally in the first 2 months of treatment. Eight patients had mild symptoms not requiring a dose reduction, 8 had significant depression requiring a dose reduction to relieve symptoms, and 7 required discontinuation of tamoxifen. We conclude that clinical depression as a side effect of tamoxifen therapy may be more common than previously believed and should be further rigorously investigated to confirm or deny our clinical impressions.

The Texas Breast Screening Project: Part I. Mammographic and clinical results.

The 1987 Texas Breast Screening Project was designed to educate women about the benefits and safety of mammographic screening. During the 2-week promotion, 109,339 women called toll-free telephone numbers to inquire about the program, and 64,459 (65%) of 99,650 eligible callers had $50 mammograms at 306 participating community radiology centers. Biopsies were obtained for 1,122 women (1.7% of those screened), and the ratio of benign to malignant biopsy results was 4.2:1. Among the women having biopsies, 214 cancers were found (3.3 cancers per 1,000 women screened). Forty-seven percent of the tumors were not palpable, 80% were smaller than 2 cm, and 72% were clinicopathologic stage 0 or I. These results show that women will respond to an invitation to attend mammographic screening, and that community radiology centers can detect large numbers of early, curable breast cancers.

Fat-suppressed three-dimensional MR imaging of the breast.

Rotating delivery of excitation off-resonance (RODEO) is a new magnetic resonance (MR) imaging pulse sequence that uses a jump return sine excitation on fat resonance to produce fat-suppressed, T1-weighted images. New three-dimensional MR imaging techniques were used to examine 57 women with abnormalities suspicious for breast cancer. MR imaging findings were compared with those of mammography in all cases and with those of other imaging techniques when appropriate. Thirty-five specimens obtained at mastectomy were analyzed with rigorous pathologic examination that included imaging of the entire breast at 5-mm incremental sections. Histologic confirmation was obtained in 76 lesions in 47 patients. MR imaging helped detect 100% of malignant lesions, whereas mammography produced 33% false-negative findings. The use of RODEO in breast imaging is in the early investigational phases, but it has potential for supplementing mammography in the diagnosis of breast cancer.

Breast cancer screening behaviors and attitudes in three racial/ethnic groups.

Data from a multiethnic sample of women participating in the American Cancer Society 1987 Texas Breast Screening Project was used to compare attitudes and behaviors related to breast cancer screening for whites, blacks, and Hispanics. In general, similar patterns of association were observed across racial/ethnic groups between a number of demographic and risk factors and prior mammography and recent clinical breast examination (CBE), although the magnitude of the associations varied somewhat across groups. Reasons for not having had prior mammography also were similar across groups, with lack of physician referral and cost cited as the two most important reasons. However, Hispanics were less likely than blacks or whites to report prior breast cancer screening, including mammography, CBE, and breast self-examination (BSE). This study demonstrated that women of different racial/ethnic backgrounds can be successfully recruited to participate in a patient-initiated, community-based program. However, this programmatic approach requires augmentation with other intervention strategies designed to reach low-income women because women with more years of education and higher family income were overrepresented in all three groups.

Design and conduct of a low-cost mammography screening project: experience of the American Cancer Society, Texas Division.

To improve compliance with recommendations for screening mammography, the American Cancer Society (ACS) Texas Division designed and conducted a media-promoted screening project in 1987. The project was planned during a 2-year period by a task force made up of physicians and lay members of ACS division committees. Radiology centers desiring to participate in the project were asked to submit information about the number of patients they could screen and their equipment, along with physics data, to a review committee. Of 306 facilities that responded, 266 (87%) passed the initial review. Thirteen facilities (4%) submitted images from two examinations using a dedicated mammography phantom, and 27 sites (9%) entered the project by agreeing to adhere to the project standards and guidelines without undergoing formal review. All facilities agreed to provide mammograms for $50 to women scheduling appointments during a 2-week media campaign in February 1987. The project generated 64,459 mammographic screening examinations. Our experience indicates that a media campaign can encourage women to have screening mammograms and that screening facilities will agree to screen a large number of women at reduced cost. This strategy, if widely applied, can improve compliance with mammographic screening recommendations and reduce breast cancer mortality.

Mammography in a mobile setting: remaining barriers.

This study examined the barriers to undergoing mammography perceived by a group of women with ready access to reduced-cost screening mammography in a mobile van at the workplace. The subject sample comprised women who made appointments for mammography at the Susan G. Komen Mobile Breast Center in Dallas. Women who underwent mammography and women who made appointments but did not undergo the examination were asked to complete a survey examining potential barriers to undergoing mammography. The group of patients surveyed were, as a whole, well educated, affluent, less than 50 years of age, and knowledgeable about breast cancer. Compliant women were more likely to have previously undergone mammography (P less than .001), to have been influenced by their physician's advice to undergo mammography (P less than .005), and to be influenced by the media than were noncompliant women (P less than .005). These findings may be useful in developing strategies to increase mammographic screening in a self-referred population.

Mammographic screening of women with increased risk of breast cancer.

Five hundred one women from Dallas County, Texas who participated in the American Cancer Society 1987 Texas Breast Screening Project were selected because of a self-reported family history of breast cancer (cases). They were matched with 501 randomly selected women from the same county with no family history (controls). Although there was a statistically significant trend with age for an increasing proportion of women to report having undergone mammography, there was no significant difference when comparing mammographic histories of cases with controls after controlling for age (31.5% versus 35.1%, P = 0.33). Significantly more cases (79%) perceived their risk for breast cancer to be moderate or greater compared with controls (54%, P less than 0.0001), but mammographic histories were not different when controlling for perceived risk. Both cases and controls cited lack of physician referral and cost as their reasons for not having undergone mammography. Women at increased risk for breast cancer (because of their family history) are not undergoing regular mammographic screening despite their self-awareness of the increase in their risk.

Breast screening compliance following a statewide low-cost mammography project.

Public health educational campaigns can attract large numbers of one-time participants, but the impact on subsequent behavior remains unstudied. The American Cancer Society Texas Division, Inc. sponsored a statewide $50.00 mammography screening project in early 1987. More than 64,000 mammograms were completed at 306 centers; 37,000 screenees answered a 31-item questionnaire. Attitudes toward screening were assessed, and screening history was recorded. Eighteen months after the project, a follow-up questionnaire was sent to 1000 screenees; 411 women returned the questionnaires. In the year following the project, 51% of the women 50 years and older reported having a subsequent mammogram. Among the women in this group who had never had a mammogram prior to 1987, 42% had screening mammography repeated in the following year. These data show that media-based public education projects can be effective mechanisms for improving and maintaining compliance with mammography screening recommendations.

Efficacy of peroperative liver function tests and ultrasound in detecting hepatic metastasis in carcinoma of the breast.

Two hundred and twenty patients with clinical stage I, II, or III carcinoma of the breast who presented for mastectomy were prospectively evaluated for hepatic metastases with abdominal sonography and routinely available liver enzymes (LE). Both abdominal ultrasound (US) and LE were assessed. There were two false-positive sonogram, both with normal enzymes, in patients with Stage I and II. There was one positive sonogram at presentation in a patient with Stage III, confirmed by needle biopsy, with a lactate dehydrogenase (LDH) elevation. The metastatic yield was low with ultrasound, but other findings were revealed. LE were not useful in the preoperative diagnosis of hepatic metastases, demonstrating a low specificity. Thirty-three patients demonstrated abnormalities of Le. Twenty-seven of 33 had elevation of a single enzyme, LDH being the most common. Three patients had an elevation of four enzymes preoperatively. Hepatic metastases were not diagnosed in these three patients preoperatively on ultrasound or biopsy. The patients were observed with physical examination (PE) and LE for a mean of 26 months. During the follow-up study, 0.9 per cent of the patients with Stage I, 3.4 per cent with Stage II and 12.5 per cent with Stage III had hepatic metastases develop. In patients with these metastases, involvement of the liver was suggested by elevated LE In 66 per cent, on PE in 42 per cent and by history in 28 per cent. LE were the first indication of liver involvement in two patients. We are in agreement with previous authors for abandonment of hepatic imaging in the preoperative assessment because of the low yield for metastases. Forty-eight thousand dollars would have have been spent on this cohort ot diagnose one instance of hepatic metastasis preoperatively. US may be efficacious in the subgroup of patients with grossly elevated LE or a PE suggestive of hepatic involvement. Those patients who demonstrate metastases by us should have histologic confirmation if treatment would thereby be altered.

Phase I trial of adjuvant chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) for stage II breast cancer.

Epirubicin is a new anthracycline with a potentially more favorable toxicity profile than the parent compound, doxorubicin. Accordingly, the feasibility and toxicity of 6 courses of adjuvant chemotherapy with cyclophosphamide (C), epirubicin (E), and 5-fluorouracil (F) were assessed in 10 patients with Stage 2 (node positive) breast cancer. Doses of C and F were 600 mg/m2 and E was 75 mg/m2. Moderate granulocytopenia (median count = 610/mm3) occurred on day 14 of the first 21 day treatment course and was the main toxicity encountered with treatment, although there were no episodes of granulocytopenic fever. Grade 3 or 4 vomiting occurred in 40% and significant alopecia in 30% of patients. Four patients experienced transient asymptomatic decreases in calculated radionuclide cardiac ejection fraction of greater than or equal to 10% but no signs or symptoms of cardiac failure were observed. If epirubicin proves to be less cardiotoxic than doxorubicin, this combination would merit further evaluation as potential adjuvant therapy for early breast cancer.

Tumor hormone receptor status and recurrences in premenopausal node negative breast carcinoma.

To ascertain the prognostic significance of tumor hormone receptor status in node negative, premenopausal patients with breast cancer, a retrospective view of 199 patients fitting these criteria was conducted. Of these 199 patients, 147 had estrogen receptor data available. There were 104 patients (71%) who were estrogen receptor negative, and 16 (15%) had developed local or distant recurrence with a median follow-up of 44 months. Five patients had died of breast cancer. Of the 43 patients who were estrogen receptor positive, there was one recurrence, and no breast cancer deaths. This difference in recurrence is statistically significant (P less than 0.01) by the log-rank probability test. Of the 17 patients with recurrent disease, 14 (82%) had primary tumors 2 cm or larger in size. If only those patients with tumors 2 cm or larger are considered, 23% (13/57) who were estrogen receptor negative and 5% (1/19) who were estrogen receptor positive recurred. This remains statistically significant (P less than 0.025). We conclude that tumor hormone receptor status and size of tumor are significant prognostic factors in identifying premenopausal, node negative women at risk for recurrent disease.