Showing papers in "Breast Journal in 2001"

Breast Conservation Therapy with Tumor Bed Irradiation Alone in a Selected Group of Patients with Stage I Breast Cancer

Abstract: Radiotherapy after breast-conserving surgery increases local control. We tested the feasibility of limited surgery with tumor bed irradiation only with 192Ir in a selected group of patients with stage I breast cancer. Twenty-five breasts in 24 women more than 60 years old with low- or intermediate-grade stage I tumors were treated with placement of interstitial catheters at the time of lumpectomy and axillary node dissection. This procedure was followed by after-loading with low-dose 192Ir to deliver 20–25 Gy to the tumor bed over 24–48 hours. There were neither local recurrences in the breast nor distant recurrences at a median follow-up of 47 months (range 25–90 months). Cosmetic appearance ranged from very good to excellent. There were no long-term complications. It is feasible to treat a select group of patients with tumor bed irradiation, using relatively low doses of interstitial irradiation, with excellent local control and no significant morbidity.

Mammary gland architecture as a determining factor in the susceptibility of the human breast to cancer.

Abstract: The developmental pattern of the breast can be assessed by determining the composition of the breast in specific lobular structures, which are designated as lobules type 1 (Lob 1), lobules type 2 (Lob 2), and lobules type 3 (Lob 3), with Lob 1 being the less developed and Lob 3 being the most differentiated or with the highest number of ductules per lobular unit. In the present work, the patient population consisted of three groups of women who underwent surgical procedures: The first group included women who underwent reduction mammoplasty (RM) for cosmetic reasons. The second group included women who underwent prophylactic subcutaneous mastectomy after genetic counseling for either carrying the BRCA-1 gene or belonging to a pedigree with familial breast cancer (FAM), and the third group included women who underwent modified radical mastectomy (MRM) for the diagnosis of invasive carcinoma. The RM group consisted of 33 women, of whom 9 were nulliparous and 24 were parous. The FAM group consisted of 17 women, of whom 8 were nulliparous and 9 were parous. The MRM group consisted of 43 women, of whom 7 were nulliparous and 36 were parous. The analysis of the lobular composition of all of the samples from the RM group, which is considered the control group, revealed that Lob 1 represented 22%, Lob 2 represented 37%, and Lob 3 represented 38%, whereas the tissue examined from the FAM and MRM groups contained a preponderance of Lob 1 at 48% and 74%, respectively, over Lob 3, which was 10% and 3%, respectively. When the results of the analysis of breast tissue were separated according to the pregnancy history of the donor, it was found that in the control group or RM, there was a significant difference in lobular composition. Nulliparous women of the RM group showed a preponderance of Lob 1 (46%) over parous women, which contained only 17%, whereas the percentage of Lob 3 in the nulliparous group was significantly lower (7%) than the parous group (48%). In the breast tissues obtained from FAM and MRM, no significant differences in lobular composition were observed, as all of the samples contained a higher concentration of Lob 1, independent of the pregnancy history. The breast tissue of FAM and MRM of parous women had a developmental pattern that was similar to that of nulliparous women of the same group and that was less developed than the breast of parous women of the control group. An important difference between the Lob 1 of the FAM group versus the control (RM) and the MRM group was that most of these lobules had thin ductules with an increase in hyalinization of the intralobular stroma manifested in the whole-mount preparation as an alteration in the branching pattern. The data suggest that the breast tissue of women with invasive cancer, as well as those from a background of familial breast cancer, have an architectural pattern different from the control or normal tissues and that the BRCA-1 or related genes may have a functional role in the branching pattern of the breast during lobular development, mainly in the epithelial stroma interaction.

Malignant phyllodes tumor.

Abstract: The study aims to evaluate the survival and prognosis of patients with malignant phyllodes tumor. Between 1982 and 1998, 37 women with malignant phyllodes tumor were treated at the Regional Cancer Center, Trivandrum. Twelve patients were recurrent. Survival was estimated using the Kaplan-Meier method. Patient, disease, and treatment factors were compared using log-rank test. The Cox-proportional hazard model was employed to identify the prognostic factors. Thirty-six patients had surgery. Twenty-five patients received postoperative radiotherapy, and 2 received chemotherapy in addition. The median follow-up was 43 months (range 1–170 months). Eight patients failed locally, and 7 of these were successfully salvaged by surgery. The 5-year overall survival was 74.2% (95% CI, 0.44 to 0.89), whereas 5-year disease-free survival was 59.6% (95% CI, 0.39 to 0.7). The margin of surgical excision was found to be the only independent prognostic factor (p = 0.003). However, patients with tumor size more than 5 cm (hazard ratio 2.9) were found to have increased hazard, whereas those receiving adjuvant radiotherapy (hazard ratio 0.6), married women (hazard ratio 0.4), and those women over the age of 35 years (hazard ratio 0.7) showed a decreased hazards. Cystosarcoma phyllodes is a rare malignancy of the female breast. Surgery with adequate margins is the primary treatment. Adjuvant radiotherapy appears to improve the disease-free survival.

Understanding mathematical models for breast cancer risk assessment and counseling.

Abstract: Chemoprevention and prophylactic surgery are effective interventions for lowering breast cancer incidence. However, these approaches are associated with risks of their own. Accurate individualized breast cancer risk assessment is an essential component of the risk/benefit analysis that must take place prior to implementing either of these strategies. Several mathematical models for estimating individual breast cancer risk have been proposed over the last decade. The Gail model is the most generally applicable model; however, it neglects family history information in second-degree relatives, treats pre- and postmenopausal breast cancer the same, and ignores personal histories of lobular neoplasia. The Claus model is a better family history model, but it does not assign any special relevance to histories of bilateral breast cancer or ovarian cancer, and neglects all of the nonfamily history information accounted for by the Gail model. BRCAPRO is a Bayesian family history model that calculates individual breast cancer probabilities based on the probability that a family carries a mutation in one of the BRCA genes. Though its treatment of family history information is more thorough than the other models, it neglects the nonfamily history risk factors accounted for by the Gail model and may not appreciate familial clustering unrelated to BRCA gene mutation. A thorough understanding of the principles of risk analysis and the available mathematical models is essential for anyone wishing to perform intervention counseling. This review describes the basic components of risk analysis, explains how the mathematical models work and compares the strengths and weaknesses of the various models. CancerGene is a software tool for running all of these models. It may be obtained without charge at http://www.swmed.edu/home_pages/cancergene.

Distress, coping, and social support among rural women recently diagnosed with primary breast cancer.

Abstract: This study examined distress, coping, and group support among a sample of rural women who had been recently diagnosed with breast cancer. We recruited 100 women who had been diagnosed with primary breast cancer at one of two time points in their medical treatment: either within a window up to 3 months after their diagnosis of breast cancer, or within 6 months after completing medical treatment for breast cancer. Their mean age was 58.6 years (SD = 11.6), and 90% were of white/European American ethnicity. Women completed a battery of demographic and psychosocial measures prior to being randomized into a psychoeducational intervention study, and then again 3 months later at a follow-up assessment. The focus of this article is on the women's self-reported psychosocial status at baseline. Many of the women experienced considerable traumatic stress regarding their breast cancer. However, this distress was not reflected in a standard measure of mood disturbance that is frequently used in intervention research (the Profile of Mood States). The average woman considered her diagnosis of breast cancer to be among the four most stressful life events that she had ever experienced. Also, women on average reported a high level of helplessness/hopelessness in coping with their cancer. On average, women felt that they "often" (but not "very often") received instrumental assistance, emotional support, and informational support. Women varied considerably in which kind of social group provided them with the most support, with as many reporting that they found the greatest support in spiritual/church groups or within their family units as with breast or general cancer groups. These results suggest that among these rural women with breast cancer, distress with the diagnosis of breast cancer must be carefully assessed, as women who are highly distressed about their breast cancer may not report general mood disturbance. Furthermore, the kinds of groups that rural women with breast cancer experience as most supportive need to be identified so that psychosocial interventions can be matched to breast cancer patients' individual needs.

Spiritual expression and immune status in women with metastatic breast cancer: an exploratory study.

Abstract: This exploratory study examined relationships between spirituality and immune function in 112 women with metastatic breast cancer. Spirituality was assessed by patient reports of frequency of attendance at religious services and importance of religious or spiritual expression. White blood cell counts, absolute numbers of lymphocytes, T-lymphocyte subsets, and natural killer cells were assessed by flow cytometry. Assessments of natural killer cell activity and delayed-type hypersensitivity responses to skin test antigens provided two measures of functional immunity. In analyses controlling for demographic, disease status, and treatment variables, women who rated spiritual expression as more important had greater numbers of circulating white blood cells and total lymphocyte counts. Upon examination of relationships with lymphocyte subsets, both helper and cytotoxic T-cell counts were greater among women reporting greater spirituality.

Breast cancer: knowledge, attitudes, and practices of female schoolteachers in lagos, nigeria

Abstract: This article examines the knowledge, attitudes, and practices of female schoolteachers concerning breast cancer. A cross-sectional survey was conducted among 200 schoolteachers randomly selected from 12 schools in Lagos, Nigeria. A self-administered questionnaire was used to investigate their knowledge about the symptoms of breast cancer, methods of diagnosis, risk factors, and breast self-examination. A response rate of 94% (188 respondents) was achieved. Eighty-five percent knew breast cancer was a serious disease, but only 53.2% knew that a breast lump was the most commonly recognized sign. Other symptoms were even less well known. Only 13.8% knew the methods of diagnosis, and knowledge of risk factors was also poor. Breast self-examination was practiced by 62% of respondents; 11% practiced it on a monthly basis, but only 25% were deemed to possess sufficient knowledge about the procedure. One-quarter of participants were categorized as possessing a satisfactory knowledge of breast cancer. The level of awareness on breast cancer is very low among this group of female schoolteachers.

Tamoxifen in the Management of Pseudoangiomatous Stromal Hyperplasia

Abstract: Pseudoangiomatous stromal hyperplasia (PASH) is a relatively uncommon histologic finding in breast specimens. The clinicopathologic spectrum of this disease entity can range from a focal nonsignificant microscopic finding to a dominant palpable breast mass. To confirm the diagnosis, a biopsy is required primarily to distinguish PASH from a low-grade angiosarcoma. The mammographic description of PASH is a round or ovoid, circumscribed or partially circumscribed mass. The sonographic feature is a hypoechoic mass. PASH is similar to a fibroadenoma in clinical and imaging features. Progressive breast enlargement associated with engorgement, cyclical breast pain, and burning sensation is of significant concern for some women. The management of the palpable mass and associated symptoms has included excisional biopsy, often leading to recurrent excisions and even mastectomy. This report documents an impressive response to tamoxifen in a patient with PASH presenting with breast enlargement, pain, and breast masses. To our knowledge, there are no reports on the use of tamoxifen or other selective estrogen receptor modulators in the management of this benign breast condition.

Her-2/neu gene amplification in low to moderately expressing breast cancers: possible role of chromosome 17/Her-2/neu polysomy.

Abstract: Overexpression of the Her-2/neu (HER2) oncogene is known to confer important prognostic and predictive value to patients with breast cancer. Controversy exists as to the best method for its determination caused primarily by the variable sensitivities of the different antibodies and interobserver differences, particularly in the group of breast cancers with borderline levels of expression of the protein product. This study was therefore designed to determine the status of the HER2 gene amplification in a group of breast carcinomas with low levels of overexpression. After an initial validation of our procedures, a series of 52 consecutive cases of formalin-fixed, paraffin-embedded breast cancers with low levels of overexpression and a series of 22 cases with no expression by immunohistochemistry were analyzed by fluorescence in situ hybridization (FISH), and the results correlated statistically. Amplification of the HER2 gene was observed in 16% of equivocal to weakly positive cases. Those that were amplified showed low levels of amplification with ratios less than 4.5 and a characteristic scattered pattern of distribution of HER2 signals in the FISH assay. In addition, heterogeneity was noted in two cases in the amplification of the HER2 gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. In cases without amplification, a statistically significant number showed chromosome 17 polysomy. In conclusion, equivocal to low levels of HER2 overexpression in breast cancers are associated, in the majority of cases, with chromosome 17 polysomy and a corresponding increase in the HER2 gene numbers. True gene amplification is present in only a minority of cases. FISH analysis should be used for confirmation of gene amplification. Prior screening and selection of appropriate immunohistochemistry-positive areas for FISH analysis may prove beneficial.

Local Recurrence of Breast Cancer in the Stereotactic Core Needle Biopsy Site: Case Reports and Review of the Literature

Abstract: Early mammographic detection of nonpalpable breast lesions has led to the increasing use of stereotactic core biopsies for tissue diagnosis. Tumor seeding the needle tract is a theorectical concern; the incidence and clinical significance of this potential complication are unknown. We report three cases of subcutaneous breast cancer recurrence at the stereotactic biopsy site after definitive treatment of the primary breast tumor. Two cases were clinically evident and relevant; the third was detected in the preclinical, microscopic state. All three patients underwent multiple passes during stereotactic large-core biopsies (14 gauge needle) followed by modified radical mastectomy. Two patients developed a subcutaneous recurrence at the site of the previous biopsy 12 and 17 months later; one had excision of the skin and dermis at the time of mastectomy revealing tumor cells locally. In summary, clinically relevant recurrence from tumor cells seeding the needle tract is reported in two patients after definitive surgical therapy (without adjuvant radiation therapy). Often, the biopsy site is outside the boundaries of surgical resection. Since the core needle biopsy exit site represents a potential area of malignant seeding and subsequent tumor recurrence, we recommend excising the stereotactic core biopsy tract at the time of definitive surgical resection of the primary tumor.

Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization.

Abstract: Isosulfan blue dye has been used with increasing frequency in localizing sentinel lymph nodes in breast cancer patients. Few alternative types of dye have been investigated. In a prospective study of 30 patients, methylene blue dye was used instead of isosulfan blue dye to localize the sentinel lymph node. The methylene blue dye localization technique was successful in 90% of patients. These results are similar to those for isosulfan blue dye. This study describes methylene blue dye localization as a successful alternative to isosulfan dye in identifying the sentinel node in breast cancer patients. The methylene blue dye technique offers a substantial cost reduction.

Lactating adenoma: a diagnosis of exclusion.

Abstract: This is a case of a large lactating adenoma which developed in a 26 year old primagravida during the third trimester of her pregnancy. The presentation was that of a grossly enlarged and engorged breast with breast erythema, warmth and tenderness. Radiologic and pathologic examinations were difficult because of the lactational changes in the breast and areas of infarcted tissue within the large tumor. Skin biopsies and core biopsies of the mass were performed to exclude malignancy. Surgical resection of the mass was necessary for definitive diagnosis. The pathology proved to be a lactating adenoma, which is the most prevalent breast mass in young pregnant females. The large size of this tumor, and the presentation of breast erythema and edema raised the possibility of inflammatory breast cancer. Following surgical resection and definitive diagnosis of this tumor, the patient required plastic surgical reconstruction of the breast because of redundant breast tissue. Although most lactating adenomas spontaneously involute, the diagnosis is not always straight-forward and surgical resection may be required for definitive diagnosis and exclusion of other pathologic processes.

Case control study of prognostic markers and disease outcome in inflammatory carcinoma breast: a unique clinical experience.

Abstract: Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast cancer. In this first-ever study the authors investigated the role of nine prognostic markers expression (estrogen receptor [ER] progesterone receptor [PR] p53 C-erB-2 epidermal growth factor receptor [EGFR] cathepsin D [CD] proliferating cell nuclear antigen [PCNA} deoxyribonucleic acid (DNA) ploidy and S-phase fraction [SPF] and disease outcome in IBC cases compared with the control group. A case control study of IBC was conducted on 40 test cases with two controls per case matching age grade and number of axillary lymph nodes sampled. During 7 years of this study 10% of all patients with breast cancer had IBC. In this study 84% of IBC cases showed positive axillary lymph nodes compared with 63% in control group. The expression of nine prognostic markers that is ER PR p53 C-erB-2 EGFR CD PCNA SPF and DNA ploidy was studied by immunohistochemistry and flow cytometry. Hormone receptor status showed an inverse correlation (p < 0.05). Among p53 C-erbB-2 ERGFR and CD in the IBC group only p53 showed a significant correlation with 70% positivity in IBC versus 48% in the control group (p < 0.05). Much higher SPF and PCNA positivity was seen in the IBC group compared with the control group (p < 0.05). DNA ploidy also showed a significant correlation compared with the control group (p < 0.05). After a median follow up of 18 months median overall survival in the IBC group was 1.8 years (range 0.6-5.8 years) compared with 3.0 years (range 2.5-7.0 years) with a p value of 0.0001. (authors)

From adjuvant therapy to breast cancer prevention: BCPT and STAR.

Abstract: The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women 35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p < 0.00001). Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided p < 0.002). In addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had no effect on the rate of ischemic heart disease. As previously shown, the rates of endometrial cancer and vascular events increased with tamoxifen. With the P-1 results establishing tamoxifen as the standard of care for the primary chemoprevention of breast cancer in high-risk women, concern over the side effects of tamoxifen has prompted a continuing search for an agent that displays a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM approved for the prevention of osteoporosis in postmenopausal women, displays antiestrogenic properties in the breast and possibly the endometrium, and estrogenic effects in the bone and on the lipid profile, suggesting it as a candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in North America. The plan is to randomize 22,000 postmenopausal women 35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events.

Tubular carcinoma of the breast: a population-based study of nodal metastases at presentation and of patterns of relapse.

Abstract: Tubular carcinoma of the breast (TCB) is a recognized histologic variant of infiltrating ductal carcinoma (IDC) and has been considered to have a comparatively favorable prognosis. However, previous studies have been based on small numbers of cases, some pure TCB and some mixed histology, or have not employed an appropriate comparison group. In this study 171 pure TCB cases and a comparison group of 386 cases with grade I (well differentiated) IDC were identified in a population-based database maintained by the British Columbia Cancer Agency (BCCA). The proportion of cases with axillary nodal involvement at presentation was lower in TCB cases than in the grade I IDC comparison group (12.9% and 23.9%, respectively; p < 0.05). Low-risk tumors (T1 and without vascular lymphatic or perineural invasion) were more prevalent in the TCB patients than in the grade I IDC patients (66.7% and 60.0%; p < 0.05). Low-risk TCB cases had a significantly lower rate of nodal metastases at presentation than low-risk grade I IDC cases (7.0% and 13.2%; p < 0.05). Kaplan–Meier and log-rank analyses indicated a statistically significantly lower rate of local recurrence in TCB cases than among IDC cases (p < 0.05) and a trend toward a lower rate of systemic relapse in TCB cases (p = 0.07). However, no difference in disease-specific survival was observed between TCB cases and grade I IDC comparisons. We conclude that the biologic behavior of TCB was more favorable than that of a comparison group of IDC cases. In view of the low incidence of axillary node metastases at presentation in the low-risk TCB subset (7%), axillary dissection may be omitted as part of the initial surgical management in these patients.

Improved lymphatic mapping technique for breast cancer.

Abstract: Breast sentinel lymph node biopsy is becoming more common. However, the best injection technique is not well established. Currently the gold standard is peritumoral injection. However, for upper outer quadrant tumors there is considerable axillary “shine through” which makes the identification of the radioactive sentinel lymph node difficult. We undertook a study to compare an injection in Sappey's subareolar plexus to the gold standard of peritumoral injection. Between December 1997 and March 1998, 85 patients with breast cancer were enrolled in the study. All patients were injected with 2 cc of normal saline containing 1.0 mCi of unfiltered technetium sulfur colloid in Sappey's subareolar plexus in the clock position of the breast cancer. In the operating room the patients underwent a peritumoral injection of 5 cc of 1% isosulfan blue. All blue and radioactive lymph nodes were identified and removed. The majority of the tumors were in the upper outer quadrant and were diagnosed by core biopsy. Only half of the patients had palpable tumors and approximately 25% had previous upper outer quadrant biopsy incisions. Peritumoral blue dye injection yielded an identification rate of 94%, with 99% of these being blue and radioactive. Three patients had radioactive lymph nodes with no blue lymph nodes identified. One of these patients had a micrometastasis. Injection in Sappey's subareolar plexus in the clock position of the tumor drained to the same sentinel lymph node as peritumoral injection. This injection technique solved the two major problems confronting the wide adoption of sentinel lymph node biopsy for breast cancer staging. First, it eliminates axillary “shine through” which will allow nonspecialist surgeons to more easily identify the radioactive axillary sentinel lymph node. Second, it allows for easier isotope injection by the technician or nuclear medicine physician, by eliminating the need for three-dimensional localization. This new technique should allow the majority of breast cancer patients who are treated by nonspecialist surgeons to be offered this less morbid, more accurate procedure.

The effectiveness of the Gail model in estimating risk for development of breast cancer in women under 40 years of age.

Abstract: Epidemiologic studies have provided information on risk factors for breast cancer. Gail and associates identified five risk factors using the Breast Cancer Detection Demonstration Project (BCDDP) population and developed a model to calculate a composite relative risk (RR). This model is commonly used to counsel women regarding their risk for breast cancer and was used by the National Surgical Adjuvant Breast Project (NSABP) for eligibility for the Breast Cancer Prevention Trial. Because the BCDDP population was composed almost entirely of women 40 years of age or older, our purpose was to evaluate the effectiveness of the Gail model in estimating the risk of breast cancer for women under 40 in the clinical setting. The Gail risk factors were assessed for 124 patients under the age of 40 treated for either ductal carcinoma in situ (DCIS) or invasive breast cancer at the Lahey Hitchcock Medical Center between 1983 and 1995. The RR was calculated using the Gail model. For comparison, two cohorts of women under the age of 40 were used: 107 randomly selected patients who underwent a breast biopsy because of a benign condition and 129 nurses from our institution who responded to a questionnaire that included reproductive and family history information as used in the Gail model. The RR calculated was the RR that existed at the time of the surgical consultation for a suspicious breast lesion. The Tarone-Ware method was used to analyze statistical significance of differences between distribution. Contingency tables were analyzed using Miettinen's modification of Fisher's exact test. No differences were found between the median RR for all groups. Only 2 of the 124 patients with breast cancer had a RR of 5 or more (the RR required to enter the Breast Cancer Prevention Trial). The distribution of age at menarche (AGEMEN) was the same for each group. No difference was found for the distribution of age at first live birth (AGEFLB) between those with breast cancer and those with a benign biopsy or the control group. The number of breast biopsies (NBIOPS) was higher in patients with a benign breast biopsy. No difference was found in the distribution of number of first-degree relatives with breast cancer (NUMREL). Overall the Gail model failed to differentiate those women about to have cancer diagnosed from two control populations. The Gail model is not useful in identifying immediate risk of breast cancer in women under 40 and should not be used for that purpose.

Who's listening? Experiences of women with breast cancer in communicating with physicians.

Abstract: The purpose of this qualitative study was to describe communication behaviors and attitudes of physicians that were most important to women living with breast cancer. Two focus group sessions were conducted, 1 month apart, involving 15 women who were members of a community-based breast cancer support group in Vancouver, British Columbia, Canada. Group dialogue was audiotaped, and notes were taken at each session by the coinvestigators, also members of the support group. Audiotapes, coinvestigators' written notes from the two focus group sessions, and the written homework assignments were used in the qualitative data analysis. Conceptual themes were identified and grouped to discern patterns within the data. The women were asked the following: (a) What were the most helpful things your doctor said or did at the time of your diagnosis? (b) What does a good intervention feel or look like? They were then asked to describe behaviors and attitudes they would like to influence in medical students who might later be communicating with women facing a diagnosis of breast cancer and to indicate which behaviors and attitudes they felt were most important. Women's positive experiences with physicians were characterized by communication based on active listening, awareness of the women's knowledge of their illness, honesty, and partnership. Physicians who showed interest in their patients as persons and who used touch to communicate caring were perceived as supportive communicators. Not surprisingly, there were similarities between the participants' positive experiences with their own physicians and the behaviors and attitudes desired in future physicians. Once again, "listening" was ranked as most important, followed by willingness to discern the individual patient's knowledge level.

Poland's Syndrome and Carcinoma of the Breast: A Case Report

Abstract: Poland's syndrome is a rare congenital anomaly that may include mammary hypoplasia and has been described in association with various malignancies. We report the case of a 42-year-old woman with unilateral Poland's syndrome who developed carcinoma in the hypoplastic breast. A review of the literature reveals no previous report of carcinoma of the hypoplastic breast with Poland's syndrome.

Biomarker assays in nipple aspirate fluid.

Abstract: The noninvasive technique of nipple aspiration as a potential source of biomarkers of breast cancer risk was evaluated. The feasibility of performing mutagenesis assays, amplifying DNA, and performing protein electrophoresis on nipple aspirate fluid was explored. A tool was developed to measure the level of discomfort, if any, from this procedure. Twenty-five healthy women (20 premenopausal and 5 postmenopausal) were enrolled. Fluid was obtained using a modified breast pump. Premenopausal women were scheduled for four to six weekly aspirations, and postmenopausal women were scheduled for one to two weekly aspirations. Mutagenesis assays were performed using the Salmonella (Ames) assay. DNA amplification of several microsatellite regions was carried out using polymerase chain reaction. Protein was quantified, and two-dimensional protein electrophoresis was performed. Overall, fluid was obtained from 80% of the women, and the level of discomfort was minimal. Acid hydrolysis of one sample resulted in mutagenicity; all six nonhydrolyzed samples were not mutagenic. The ability to amplify DNA ranged from 34% to 96%, depending on length of the microsatellite region examined. The average protein concentration was 71 microg/mL. Two-dimensional protein electrophoresis was successfully performed on samples from two subjects. Nipple aspiration is a simple technique and is easily learned and well tolerated, which yields a reagent useful for a variety of investigations. This technique may facilitate the identification and application of biomarkers for future breast cancer risk assessment and chemopreventive protocols.

Biopsy technique has no impact on local recurrence after breast-conserving therapy.

Abstract: Image-guided core needle breast biopsy (IGCNBB) is an incisional biopsy technique that has been associated with tumor cell displacement. Theoretically tumor cell displacement may affect local recurrence rates in patients treated with breast-conserving therapy (BCT). We performed a study to determine if the biopsy method impacted local control rates following BCT. Patients with nonpalpable breast cancer (invasive and intraductal) diagnosed at our institution and treated with BCT between July 1993 and July 1996 were selected to provide a follow-up period in which the majority of local recurrences should be detected. Patients were divided into two groups based on their method of diagnosis. Group I patients were diagnosed by IGCNBB and group II patients were diagnosed by wire localized excisional breast biopsy (WLEBB). Factors potentially affecting local recurrence rates were retrospectively reviewed. Two hundred eleven patients were treated with BCT, 132 were diagnosed by IGCNBB and 79 by WLEBB. The two patient groups were similar when compared for prognostic factors and treatment. All patients' BCT included histologically negative margins. There were 4 (3.0%) local recurrences in Group I at a median follow-up of 44.4 months and 2 (2.5%) local recurrences in group II at a median follow-up of 50.1 months. This difference was not significant. Breast cancer patients diagnosed by IGCNBB can be treated by BCT with acceptable local control rates. Additional surveillance of our institutional experience and others' is mandatory to validate IGCNBB as the preferred biopsy method for nonpalpable mammographic abnormalities.

The potential use of intensity modulated radiotherapy (IMRT) in women with pectus excavatum desiring breast-conserving therapy

Abstract: The purpose of this study was to determine if intensity modulated radiation therapy (IMRT) offers a better treatment plan compared to conventional radiotherapy for patients with pectus excavatum desiring breast-conserving therapy and to assess the feasibility of simultaneous modulated accelerated radiation therapy (SMART) boost. A patient with pectus excavatum desired breast-conserving therapy for her early stage breast cancer. She underwent lumpectomy and axillary lymph node dissection followed by chemotherapy. She was then referred for radiotherapy. A breast board (Med-Tec) with aquaplast body cast was used to limit the movement of the patient, chest wall, and breasts before planning a computed tomography (CT) scan. IMRT including dose-volume histogram (DVH) was compared to that of the conventional plan using parallel opposed tangential beams with a 15-degree wedge pair. Forty-five gray was prescribed to the whole breast to each plan, while 50 Gy was prescribed to the tumor bed using IMRT with SMART boost in 25 fractions over 5 weeks. The coverage of the whole breast was adequate for both plans. IMRT allowed a more homogeneous dose distribution within the breast at the desired dose range. With IMRT there is less volume of ipsilateral lung receiving the radiation dose that is above the tolerance threshold of 15 Gy when compared to that of the conventional plan. However, there is more volume of surrounding normal tissues (the heart, spinal cord, and contralateral breast and lung) receiving low-dose irradiation when IMRT was employed. SMART boost was feasible, allowing a mean dose of 57 Gy to be delivered to the tumor bed simultaneously along with the rest of the breast in 5 weeks. IMRT is feasible in treating early breast cancer patients with pectus excavatum by decreasing the ipsilateral lung volume receiving high-dose radiation when compared to the conventional method. SMART boost shortens the overall treatment time that may have potential radiobiological benefit.

In situ duct carcinoma of the breast: clinical and histopathologic factors and association with recurrent carcinoma.

Abstract: There has been a recent increase in the diagnosis of in situ duct carcinoma of the breast (DCIS) as a result of mammographic screening. DCIS is heterogeneous in appearance and likely in prognosis. There is no generally accepted model to predict progression to invasive carcinoma. We investigated the prognostic effect of clinical presentation and pathologic factors for women diagnosed with primary DCIS. A cohort of 124 patients was accrued between 1979 and 1994 and was followed to 1997; 78 had DCIS detected mammographically, and 88 underwent lumpectomy alone. In this article, we provide details about characteristics affecting the choice of primary therapeutic modality, and we examine the effects of factors on progression for the two patient subgroups. Presentation with bloody nipple discharge was associated with a significant increase in DCIS recurrence (p = 0.07). The pattern of duct distribution was important: DCIS in which the involved ducts were more widely separated had a significantly greater recurrence of DCIS than when the involved ducts were more concentrated (p = 0.08 for mammographically detected DCIS, p = 0.07 for patients who underwent lumpectomy alone). For mammographically detected DCIS, younger patients had more DCIS recurrence (p = 0.07). We found considerable heterogeneity in nuclear grade; 50% of patients exhibited more than one grade. Nuclear grade, necrosis, and architecture were not significantly associated with either recurrence of DCIS or development of invasive carcinoma. Longer follow-up will allow further evaluation of the prognostic relevance of the factors assessed.

Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast.

Abstract: Epithelial mucins are glycoproteins secreted by epithelial cells and their carcinomas. At least nine mucin genes have been identified, and their products (MUC1–MUC9) are expressed in various epithelia. MUC1 is a mucin expressed in breast epithelial cells, whereas MUC2 and MUC3 are primarily intestinal mucins. Although MUC1 and MUC2 expression has been documented in invasive ductal carcinoma of the breast, mucin expression in pure ductal carcinoma in situ (DCIS) has not been investigated. Sixty-one of 105 cases of DCIS without coexisting infiltrating carcinoma diagnosed during a 30-month period were selected as having sufficient tissue for study. Paraffin-embedded tissue sections were stained using immunohistochemical techniques with mouse monoclonal anti-MUC1, anti-MUC2, and rabbit-specific polyclonal anti-MUC3 antibodies. Immunoreactive epitopes of MUC1, MUC2, and MUC3 were expressed in DCIS in 61, 19, and 16 of 61 cases, respectively. MUC2 and MUC3 staining intensity in DCIS was markedly less than that observed for MUC1. Luminal and/or cytoplasmic patterns of staining were observed for MUC1. MUC2 and MUC3 showed only cytoplasmic staining. Cytoplasmic-only staining of MUC1 was associated with a higher grade of DCIS. Any MUC2 staining was also associated with a higher grade of DCIS. Coexpression of MUC2 and MUC3 was present in only 6 of 61 cases, and MUC3 staining was unrelated to the grade of DCIS. Cytoplasmic expression of MUC1 and MUC2 appears to be associated with a higher grade of DCIS. MUC3 expression appears to be independent of grade and expression of MUC1 and MUC2. The relationship of mucin expression and grade warrants further study.

The inverse relationship between microvessel counts and tumor volume in breast cancer.

Abstract: Angiogenesis has emerged as an indicator of metastatic potential in invasive breast cancer. Exponential tumor growth and the appearance of metastasis are observed as new microvessels form. We postulated that the relevance of angiogenesis would be enhanced if analyzed as a function of tumor volume rather than greatest diameter alone and that microvessel counts would proportionately increase as does volume. Since tumors are three-dimensional solids, volume was calculated using the formula for an ellipsoid, V = pi/6 (a x b x c). Sixty-four tumors < or = 2.5 cm were studied and analyzed in 5 mm incremental ranges. Mean microvessel counts did not vary significantly among these tumor size groups. However, analysis of microvessel counts as a function of tumor volume decreased from 947.1/cm3 (0-0.5 cm) to 18.1/cm3 (2.1-2.5 cm), a greater than 50-fold difference. High microvessel density in small cancers supports the notion of metastasis as an early event, making these small tumors perhaps ideal targets for antiangiogenic agents.

Diagnosis of Metachronous Contralateral Breast Cancer

Abstract: The purpose of this study was to compare the characteristics of primary breast cancers (PBCs) and metachronous contralateral breast cancers (MCBCs). Between 1984 and 1996, 236 women treated with curative intent for PBC who developed a MCBC >6 months after initial diagnosis (without previous evidence of distant metastases) were retrospectively evaluated for clinical and pathologic characteristics and method of diagnosis of their tumors. There were more noninvasive cancers among the MCBCs than the PBCs (11.4% and 5.1%, respectively, p < 0.02). Among the invasive cancers, the mean size of the MCBCs was smaller than the PBCs (1.94 versus 2.55 cm, p < 0.001). MCBCs were more likely than PBCs to be mammographically detected (46.2% versus 19.9%, p < 0.001). Tumor size was correlated with the method of diagnosis. The mean tumor size was 1.39, 2.02, and 2.69 cm for mammogram-, physician-, and patient-detected tumors, respectively. Among patients having axillary lymph node dissections, mammogram- and physician-detected tumors were less likely to have lymph node metastases than patient-detected tumors (22.0% versus 41.2%, p < 0.005). Regular follow-up of breast cancer patients diagnoses MCBCs when they are smaller and less likely to have nodal metastases than PBCs mainly because of early mammographic detection.

Mammographic appearance of ductal carcinoma in situ does not reliably predict histologic subtype.

Abstract: Histologic subtypes of ductal carcinoma in situ (DCIS) have been correlated with disease prognosis. There are conflicting reports on whether the grade of DCIS can be predicted by the morphology of calcifications seen on mammography. We undertook this study to determine whether the grade of DCIS can be reliably and accurately determined by mammography prior to excisional biopsy. Ninety consecutive cases of DCIS from 1993 to 1996 were identified, of which 75 cases had mammograms available for review. Any lesion with invasion was excluded. The mammogram showed only a mass in 10 of 75 cases, a mass and calcifications in 3 of 75 cases, and calcifications alone in 62 of 75 cases. Three board-certified radiologists with special expertise in mammography reviewed and categorized the mammographic findings as well, intermediate or poorly differentiated DCIS without knowledge of the histologic diagnosis. Histologic grading was performed without knowledge of the mammographic finding. Receiver operating curves (ROCs) were computed for each of the radiologists. For microcalcifications, the ROC comparisons of the radiologists' opinions of tumor grade and random chance were not significantly different. In those cases with available magnification views, the grade assessment did not change significantly. If only a mass was present on mammography, well-differentiated DCIS was the predominant histologic subtype. A histologic grade of DCIS cannot accurately be determined prospectively based on the mammographic appearance of microcalcifications. However, if only a mass is present, this is more likely to represent well-differentiated DCIS.

Locally advanced breast cancer: is surgery necessary?

Abstract: A retrospective analysis of the treatment of locally advanced breast cancer (LABC) was undertaken at Stanford Medical Center to assess the outcome of patients who did not undergo surgical removal of their tumors. Between 1981 and 1998, 64 patients with locally advanced breast cancer were treated with induction chemotherapy, radiation with or without breast surgery, and additional chemotherapy. Sixty-two (97%) patients received cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) induction chemotherapy. Induction chemotherapy was followed by local radiotherapy in 59 (92%) patients. Based on the clinical response to chemotherapy and patient preference, 44 (69%) patients received no local breast surgery. Radiotherapy was followed by an additional, non-doxorubicin-containing chemotherapy in all patients. The mean age of patients was 49 years. Of the 65 locally advanced breast cancers in 64 patients, 26 (41%) were stage IIIA, 35 (55%) were stage IIIB, and 4 (6%) were stage IV (supraclavicular lymph nodes only). Response to induction chemotherapy was seen in 59 patients (92%), with 29 (45%) achieving a complete clinical response and 30 (47%) a partial clinical response. With a mean follow-up of 51 months (range 7-187 months), 43 patients (67.2%) have no evidence of recurrent disease. Eight (12.5%) have recurred locally, and 21 (32.8%) have recurred with distant metastasis. Actuarial 5-year survival is 75%, disease-free survival is 58%, and local control rate is 87.5%. These data indicate that the routine inclusion of breast surgery in a combined modality treatment program for LABC does not appear necessary for the majority of patients who experience a response to induction chemotherapy.

Hamartoma of the breast in a man: first case report.

Abstract: Mammary hamartomas were reported in 0.7% of all benign tumors of the female breast. Histologically breast hamartomas contain lobular breast tissue with various degrees of fibrous, fibrocystic, and adipose tissue. Rare types include muscular (myoid) and cartilage (chondroid) hamartomas. We report a case of muscular hamartoma in a man. A 36-year-old man was admitted to the psychiatric unit with the diagnosis of schizophrenia. The patient complained of a slowly growing mass in his left breast. He denied any discharge from the nipple, but he complained of itching. A 2 cm × 3 cm nontender mass was palpable. There was no evidence of axillary lymphadenopathy. A needle aspiration was nondiagnostic. The excisional biopsy specimen revealed fatty tissue which was edematous and hemorrhagic. Microscopically it showed multiple bundles of muscles organized randomly. Myoid hamartoma was the diagnosis. Mammary hamartoma is considered a female tumor exclusively. Myoid hamartoma has been reported previously in 25 women. We report a myoid hamartoma in a man and, to our knowledge, it is the first and only such case to be reported.

Ductal carcinoma in situ and atypical ductal hyperplasia of the breast diagnosed at stereotactic core biopsy.

Abstract: Stereotactic core needle biopsy (SCNB) allows specific histopathologic diagnoses to be made without surgery and has been demonstrated to be an accurate, cost-effective method of diagnosing breast disease, particularly nonpalpable lesions. However, recent studies have concluded that the diagnosis of atypical ductal hyperplasia (ADH) by means of SCNB has resulted in nearly equal odds that a coexisting malignant lesion will be missed. Furthermore, others have concluded that SCNB diagnosed as DCIS cannot reliably indicate the absence of tumor invasion in surgical excision. Between 1993 and 1998, 1,221 consecutive SCNB of mammographically identified lesions were performed using a 14-gauge automated device with an average of 5.3 cores obtained per lesion. ADH was identified in 19 (1.6%) lesions and DCIS in 89 (7.3%). Surgical biopsy was performed in 89 of these patients and histopathologic results from SCNB and surgical biopsies were reviewed and correlated. In 12 cases of ADH diagnosed by SCNB, surgical biopsy showed ADH in 8 (67%) cases and DCIS in the other 4 (33%) cases. In 77 cases of DCIS diagnosed by SCNB, a surgical biopsy showed DCIS in 55 (71%) cases, 6 more cases (8%) had DCIS with focal microinvasion, and 15 (19%) had invasive ductal carcinoma. In one case no residual tumor was found at surgery. In the author's patient population, the diagnosis of ADH at SCNB indicates high probability of DCIS or residual ADH in the surgical biopsy. The diagnosis of DCIS at SCNB is confirmed in the majority of surgical biopsies; however, a significant number of cases may show microinvasion or invasive carcinoma.