Preoperative chemotherapy and sentinel lymphadenectomy for breast cancer.

BACKGROUND: Sentinel lymphadenectomy (SL) for breast cancer is becoming the standard of care for selected patients treated by experienced surgeons. One of the few contraindications for performing SL alone is prior chemotherapy (PC). There are, however, no data to support that PC interferes with the ability of the sentinel node to predict the presence of disease in the remaining axillary lymph nodes. The goal of this study was to determine the effect of PC on patients undergoing SL for breast cancer. METHODS: A multicenter trial was organized in 1997 to evaluate the diagnostic accuracy of SL in patients with breast cancer. Investigators were recruited after attending a course on the technique of SL. Technetium-99 and isosulfan blue were injected into the peritumor region and a gamma probe was used to aid identification of the sentinel nodes. The only exclusion criteria for entrance into the trial were palpable or suspicious axillary lymph nodes. A total of 968 patients were enrolled in the trial. Twenty-nine patients were treated with PC and compared with 939 patients not receiving PC. RESULTS: The overall, sentinel node identification rate for the PC patients was 93% (27 of 29) compared with 88% (822 of 939) for patients not treated with PC. There were no false negatives in those patients receiving PC compared with a 13% (25 of 193) false negative rate in those patients not receiving PC. The mean tumor size was 1.4 cm for the PC group and 0.6 cm for the remaining patients (P <0.005). The mean number of sentinel nodes found was 2.0 for the non-PC group and 2.5 for the PC group (not significant). As expected, a higher proportion of patients had positive axillary nodes in the PC group (52%, 15 of 29) compared with the remaining patients (21%, 200 of 939). CONCLUSION: In this small group of patients, PC did not adversely impact the false negative or identification rate. Most patients receiving chemotherapy have larger tumors and a higher chance of harboring metastatic disease but a significant group of these patients (48%) without metastases can potentially be spared an axillary node dissection.

Comparison of intradermal and subcutaneous injections in lymphatic mapping.

BACKGROUND: Sentinel node biopsy (SNB) for melanoma, with its intradermal (ID) injection, has a higher success rate than SNB for breast cancer, which is typically performed with a subcutaneous (SC) or peritumor injection. It is hypothesized that this is in part due to a slower transit time of lymphatic mapping agents through the parenchymal lymphatics of the breast. No study has investigated differences in transit time between different tissues to account for this clinical observation. The goal of the study was to compare transit time between ID and SC injections with common agents used in lymphatic mapping. METHODS: Four injection sites on five domestic pigs were used. Sites were bilateral and included cervical, forelimb, hindlimb, and flank areas. Agents included technetium sulfur colloid (Tc99, filtered and unfiltered), isosulfan blue (IB) dye, and fluorescein (FL) dye. At each site both ID and SC injections were made and the transit time to reach the sentinel node was recorded. The transit time differences were calculated per centimeter distance from the draining lymph node basin. RESULTS: Sentinel nodes were identified draining all sites and found to be hot, blue, or fluorescent (using a Wood's lamp for identification). The cervical and forelimb injection sites drained to the same cervical lymph node basin and both SC and ID injection sites drained to the same sentinel node. Similarly, the hindlimb and flank injection sites both drained to inguinal lymph node basins. The slowest transit time occurred with Tc99 injected SC and the fastest occurred with Tc99 injected ID, whereas both FL dye and IB traveled rapidly to the sentinel node whether injected SC or ID. Large differences were found using unfiltered Tc99 depending on its injection ID (2.7 s/cm +/- 0.5) vs SC (249 s/cm +/- 14.7, P = 0.008). CONCLUSIONS: Tc99 ID injections were significantly faster than SC injection. The slowest and fastest SC injection agents were unfiltered Tc99 and IB, respectively. Dermal injections provide faster transit of lymphatic agents and may improve the identification rate when applied to patients with breast cancer.

Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye.

OBJECTIVE: To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). SUMMARY BACKGROUND DATA: Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. METHODS: Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. RESULTS: Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. CONCLUSIONS: This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation.

Influence of socioeconomic and cultural factors on racial differences in late-stage presentation of breast cancer.

CONTEXT: Breast cancer mortality is higher among African American women than among white women in the United States, but the reasons for the racial difference are not known. OBJECTIVE: To evaluate the influence of socioeconomic and cultural factors on the racial difference in breast cancer stage at diagnosis. DESIGN: Case-control study of patients diagnosed as having breast cancer at the University Medical Center of Eastern Carolina from 1985 through 1992. SETTING: The major health care facility for 2 rural counties in eastern North Carolina. SUBJECTS: Five hundred forty of 743 patients with newly diagnosed breast cancer and 414 control women from the community matched by age, race, and area of residence. MAIN OUTCOME MEASURES: Breast cancer stage at diagnosis. RESULTS: Of the 540 patients, 94 (17.4%) presented with TNM stage III or IV disease. The following demographic and socioeconomic factors were significant predictors of advanced stage: being African American (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.9-4.7); having low income (OR, 3.7; 95% CI, 2.1-6.5); never having been married (OR, 2.9; 95% CI, 1.4-5.9); having no private health insurance (OR, 2.5; 95% CI, 1.6-4.0); delaying seeing a physician because of money (OR, 1.6; 95% CI, 1.1-2.5); or lacking transportation (OR, 2.0; 95% CI, 1.2-3.6). Univariate analysis also revealed a large number of cultural beliefs to be significant predictors. Examples include the following beliefs: air causes a cancer to spread (OR, 2.8; 95% CI, 1.8-4.3); the devil can cause a person to get cancer (OR, 2.1; 95% CI, 1.2-3.5); women who have breast surgery are no longer attractive to men (OR, 1.9; 95% CI, 1.1-3.5); and chiropractic is an effective treatment for breast cancer (OR, 2.4; 95% CI, 1.4-4.4). When the demographic and socioeconomic variables were included in a multivariate logistic regression model, the OR for late stage among African Americans decreased to 1.8 (95% CI, 1.1 -3.2) compared with 3.0 (95% CI, 1.9-4.7) for race alone. However, when the belief measures were included with the demographic and socioeconomic variables, the OR for late stage among African Americans decreased further to 1.2 (95% CI, 0.6-2.5). CONCLUSIONS: Socioeconomic factors alone were not sufficient to explain the dramatic effect of race on breast cancer stage; however, socioeconomic variables in conjunction with cultural beliefs and attitudes could largely account for the observed effect.

Coming to terms with advanced breast cancer: black women's narratives from eastern North Carolina.

This paper analyzes in-depth interviews with 26 black women who entered the medical system in rural North Carolina with advanced breast disease. In these narratives, women draw on multiple sources of knowledge in order to come to terms with the diagnosis of breast cancer--a biomedically-defined disease that they often refuse to acknowledge or accept. The analysis demonstrates how women relate the meaning of their individual episodes of illness to one or more of the following sources of knowledge: an indigenous model of health emphasizing balance in the blood, popular American notions about cancer, and particular biomedical conceptions about breast disease and its treatment. These narratives provide an important window into the processes involved when individuals attempt to adapt personal experience to pre-existing cultural models, modify such models in the light of new information, and confront conflicts in their own interpretations of the meaning of a single episode of illness.

Difficulties in diagnosis of carcinoma of the breast in patients less than fifty years of age.

Delay in diagnosis of carcinoma of the breast is a significant cause of medical malpractice suits in the United States. Although less than one-third of the patients with carcinoma of the breast are less than 50 years of age, more than two-thirds of these suits involve women less than 50 years of age. To see whether or not there are medical factors that make diagnosis in young women more difficult, we reviewed all patient visits to the East Carolina University (ECU) Breast Clinic between 1 January 1988 and 30 June 1991. Women less than 50 years of age had many more patient visits (1,567 versus 838 visits) and many fewer carcinomas detected (38 versus 100 visits) than women who were more than 50 years old. The sensitivity and positive predictive value of mammography were significantly lower in young women than older women (68 versus 91 percent, p < 0.005, and 28 versus 53 percent, p < 0.001, respectively). Physical examination in young women was also less satisfactory. Tumors were more ill-defined and the percent that were easily palpable were significantly lower (45 versus 72 percent, p < 0.01). Furthermore, there was a basic difference in the reason tumors were not palpable in each age group. In older women, tumors were nonpalpable because they were small (mean size 1.0 versus 4.1 centimeters, p < 0.01), whereas in younger women, the non-palpable tumors were large (mean size 4.0 versus 3.4 centimeters), suggesting that they were not palpable because of background mammary density or diffuse growth pattern rather than size. Data from the Breast Cancer Detection Demonstration Project were analyzed and also suggested that carcinomas are more difficult to diagnose in young women. The percent of carcinomas that were not detectable by either mammogram or physical examination were inversely proportional to age and ranged from 36 percent at 40 years of age to 9 percent at 75 years of age. In addition, data from Blue Cross and Blue Shield and the ECU Breast Clinic indicated that it costs at least twice as much to diagnose each carcinoma in women less than 50 years of age. In conclusion, we believe that currently available techniques for diagnosis of carcinoma of the breast are not satisfactory for women less than 50 years of age and that this, rather than physician error, may account for the large number of malpractice suits in this age group.

Increasing mammography utilization: a controlled study.

BACKGROUND: Despite the effectiveness of breast cancer screening for women older than 50 years of age, only about one third of these women in the United States receive annual mammography. PURPOSE: This study was designed to determine if a community-wide intervention could increase use of mammography screening for breast cancer. Secondary end points were determination of changes in women's knowledge and attitudes toward mammography and physicians' self-reported screening practices. METHODS: We conducted a controlled study from January 1987 through January 1990 in two eastern North Carolina communities--New Hanover County (the experimental community) and Pitt County (the control community). Before development and implementation of the intervention program in New Hanover County and after the program had been in operation for 1 year, 500 women of ages 50-74 years and all primary-care physicians in each community were interviewed by telephone. In these interviews, we determined the use of mammography for breast cancer screening and the knowledge and attitudes about it. We also established the number of screening mammograms performed in 1987 and 1989 in each county and reviewed medical records to determine the percentage of women the physicians had referred for mammograms. RESULTS: The percentage of women who reported receiving a mammogram in the previous year increased from 35% to 55% in the experimental community and from 30% to 40% in the control community (difference of differences, 10%; P = .03 after adjustment for race, education, age, and having a regular doctor; 95% confidence interval, 1%-18%). Increases were greater in New Hanover County regardless of age, race, income, and education. However, the increase was less for Black women than for White women, both overall and in most demographic subgroups. The total number of mammograms performed increased 89% in the experimental community and 45% in the control community. Women's knowledge about mammography changed little, but the intention to get a mammogram increased 30% in New Hanover County, compared with a 17% increase in Pitt County--a statistically significant difference (P < .01). Physician reports and medical record reviews in the two communities showed similar increases in the number of mammograms ordered. CONCLUSIONS: A community-wide effort to increase use of breast cancer screening was successful, but more work must be done to reach the National Cancer Institute's goal of annual mammograms for 80% of women of ages 50-74.

Mammography and age: are we targeting the wrong women? A community survey of women and physicians.

To determine mammography use among women with a broad range of ages, the authors surveyed women aged 30 to 74 years and physicians practicing primary care in two eastern North Carolina counties. Twenty-five percent of women in their 30s had ever had a mammogram, and 34% intended to have one in the coming year. From 45% to 52% of women in their 40s, 50s, and 60s had ever had a mammogram, and 55% to 57% intended to have one in the next year. Thirty-seven percent of women aged 70 to 74 years had ever had a mammogram, and 40% intended to have one in the following year. Nineteen percent of physicians reported screening nearly all women aged 30 to 39 years, and 14% screened few women aged 50 to 74 years. Younger women were more worried about breast cancer than older women and assessed their risk as higher, attitudes that were generally associated with higher mammography utilization. These community surveys suggest that mammography use may be excessive among younger women; older women continue to be underscreened.

Fine-needle aspiration cytology of breast masses in pregnant and lactating women.

Eleven pregnant women with breast masses that arose during pregnancy or in the postpartum period underwent fine-needle aspiration biopsies. Cytologic examination demonstrated a spectrum of morphologic features, including (1) a pattern of dissociated epithelial cells stripped of their cytoplasm along with small clusters of cells having a frayed secretory type of cytoplasm; (2) larger epithelial groups with nuclear pleomorphism, prominent irregular nucleoli, and abundant vacuolated cytoplasm; (3) cellular smears, often with an inflammatory background and proteinaceous debris; and (4) microtissue fragments showing features of lobular hyperplasia. This article illustrates the clinical utility of fine-needle aspiration biopsy in evaluating breast masses in pregnant and lactating women and discusses the potential hazards for a false-positive diagnosis of malignancy in these patients.

Intraoperative video panendoscopy for diagnosing sites of chronic intestinal bleeding.

Intraoperative video panendoscopy was performed in 14 patients with chronic, recurrent gastrointestinal bleeding. All of the study patients had undergone extensive and expensive diagnostic testing including multiple radiographic contrast studies of the gastrointestinal tract, upper and lower endoscopy, nuclear bleeding scans, and selective mesenteric angiography without definition of the bleeding source. Intraoperative video panendoscopy, employing a segmental advance and look technique, allowed visualization and transillumination of the entire gut and identified mucosal disease in 13 patients (93 percent). Angiodysplasia of the colon and small intestine was the most common pathologic finding. Intraoperative video panendoscopy significantly influenced the operation performed in 13 patients (93 percent). Postoperative complications were minimal, with none being directly attributable to intraoperative video panendoscopy. Bleeding was totally controlled in 10 patients (71 percent) during a mean follow-up period of 25 months. Intraoperative video panendoscopy is a valuable technique for assisting in the management of the patient with recurrent gastrointestinal bleeding.

The triage role of fine needle aspiration biopsy of palpable breast masses. Diagnostic accuracy and cost-effectiveness.

A total of 219 fine needle aspiration (FNA) biopsies of the breast were performed during the period 1983 to 1985 at a tertiary medical center. The series consisted of 215 women (98.2%) and 4 men (1.8%), with an are range of 14 to 90 years (mean of 46.5 years). Histologic confirmation (93 cases) or clinical follow-up for up to two years was obtained. The sensitivity of the FNA procedure was 82.2%, its specificity was 98.8%, and the overall efficiency of the test was 95.4%. The false-negative rate was 4.4%, with no false-positive diagnoses for the primary diagnosis of breast carcinoma. We have found that one of the major advantages of FNA biopsy is that it lowers costs by allowing the surgeon to triage which patients should have an outpatient excisional biopsy under local anesthesia and which patients should have a one-stage inpatient procedure with frozen section confirmation. For this triage role, suspicious diagnoses (3.2%) were included in the positive group and atypical (1.8%) and insufficient diagnoses (6.8%) in the negative group. Taking into account the FNA biopsy cost of $75, the procedure resulted in a savings per case of $262 over the cost that would have occurred if all cases had had routine inpatient biopsy and $154 per case over the cost that would have occurred with routine outpatient biopsy of all cases. Our results indicate that FNA breast biopsy is a diagnostically accurate and economical triage procedure, even when followed by an excisional or frozen-section biopsy for confirmation. The use of FNA biopsy could be expanded to a greater number of medical centers and decrease the potential for false-positive diagnoses by combining FNA biopsy with frozen-section confirmation.

Fine needle aspiration cytology of subareolar abscess of the breast. Spectrum of cytomorphologic findings and potential diagnostic pitfalls.

The cytomorphologic findings of eight cases of subareolar abscess of the breast diagnosed by fine needle aspiration (FNA) biopsy are presented. A spectrum of cytologic findings was appreciated, including diagnostic anucleated squames associated with numerous neutrophils, keratinous debris, cholesterol crystals, parakeratosis and strips of squamous epithelium. A foreign-body reaction, with sheets of histiocytes and multinucleated foreign-body-type giant cells, was noted in some of the cases. Potential pitfalls for a false-positive diagnosis of malignancy included the presence of groups of atypical ductal cells, squamous atypia and fragments of exuberant granulation tissue. Seven of the eight cases had complete surgical excision of the lesion, which demonstrated the characteristic findings of dilated lactiferous ducts undergoing squamous metaplasia with rupture and surrounding extensive acute and chronic inflammation with foreign-body reaction. With recognition of the FNA cytologic findings of subareolar abscess of the breast, a specific diagnosis can be rendered, which then allows different treatment modalities depending on the stage of the lesion. Appreciation of the spectrum of cytologic features will enable the pathologist to make the correct diagnosis and thereby avoid potential pitfalls that can possibly lead to a false-positive diagnosis of malignancy.

Cost-effectiveness of fine needle biopsy of the breast.

Although fine needle aspiration (FNA) biopsy of the breast has been shown to be a safe and accurate technique, many surgeons question whether it is reliable enough to replace excisional biopsy. If FNA biopsy is followed by excisional biopsy for confirmation, it would seem that the cost of diagnostic work-up would be increased. In this study, however, the authors show that the major economic benefit of FNA biopsy is not that it replaces excisional biopsy, but that it allows the surgeon to triage which patients should have a 1-stage inpatient procedure with frozen section and which patients should have an excisional biopsy as an outpatient under local anesthesia. Over the past 2 years, the average cost at the East Carolina University School of Medicine of excisional outpatient biopsy (negative) was +702 +/- 348; inpatient biopsy (negative) was +1410 +/- 262; inpatient 1-stage procedure (positive) was +4135 +/- 361; and outpatient biopsy (positive) followed by inpatient procedure was +4822 +/- 586. The authors' last 100 FNA biopsies were read as 23 positive, three suspicious, 65 negative, and nine insufficient. There were no false-positives and four false-negatives, for a sensitivity of 87%, specificity of 100%, and accuracy of 96%. Using the above figures, it is possible to calculate the cost per case if all 100 cases had been biopsied by the 1-stage inpatient technique (+2227), by the 2-stage outpatient method (+1938), or guided by the FNA biopsy where positive and suspicious readings are followed by an inpatient 1-stage procedure and negative and insufficient readings followed by an outpatient 2-stage procedure (+1759). Since the FNA biopsy costs +75, it resulted in a savings per case of +393 over routine inpatient biopsy and +104 per case over routine outpatient biopsy. Computer analysis revealed that the FNA biopsy would still be economically favorable if the sensitivity of the test fell as low as 37%, the specificity as low as 80%, or if the percentage of cases of cancer in the population biopsied fell as low as 13%. Since FNA biopsy is cost effective even when followed by an excisional or frozen section biopsy for confirmation, it would be safe and reasonable to expand its use to smaller hospitals where the personnel may be initially less experienced with the technique.

Effect of cyclophosphamide on mice bearing methylcholanthrene-induced fibrosarcomas.

Mice bearing large methylcholanthrene-induced fibrosarcomas lost the ability to respond in vitro to mitogen stimulation and to specifically neutralize autologous tumor cells in vivo. This depressed immune capability was due to active suppression, since spleen cells from advanced tumor-bearing mice could suppress the mitogen response of normal spleen cells and could inhibit tumor rejection when adoptively transferred to mice previously immunized against the tumor. Treatment with cyclophosphamide (CY) was found to affect the immune capability of the host, in addition to have a direct effect on the tumor. The number of cells in the lymph nodes and spleen, as well as their response to concanavalin A and lipopolysaccharide (but not phytohemagglutinin), decreased initially but returned to normal by Day 14. Most importantly, when CY was administered one day after tumor inoculation, the treated animals developed the ability to neutralize tumor at the same time as untreated controls but retained this capability as the tumors became advanced. Treatment with a single dose of CY as late as 11 or 20 days after tumor inoculation maintained or restored the tumor-neutralizing capacity of spleen cells. CY appears to alter the antitumor response of the host by inhibiting both cytotoxic and suppressor cells, but the cytotoxic cells recover rapidly, whereas the suppressor cells do not.