Lymphedema: current issues in research and management.

Lymphedema is a common and troublesome problem that can develop following breast cancer treatment. As with other quality-of-life and nonlethal conditions, it receives less research funding and attention than do many other areas of study. In 1998, an invited workshop sponsored by the American Cancer Society reviewed and evaluated the current state of knowledge about lymphedema. Recommendations and research initiatives proposed by the 60 international participants are presented in the conclusion section of the article, following a summary of current knowledge of the anatomy, physiology, detection, and current treatment of lymphedema. The etiology of lymphedema is multifaceted; all of the factors that contribute to the condition and the nature of their interaction have not yet been identified. To compound the problem, methods of assessing the degree of arm and hand swelling vary and are not agreed upon, and reliable methods of assessing the functional impact of lymphedema have not yet been developed. In the absence of a cure for lymphedema, precautions and prevention are emphasized. Current treatments include elevation, elastic garments, pneumatic compression pumps, and complete decongestive therapy; surgical and medical techniques remain controversial. Elements and details of these treatments are described.

Tubular carcinoma of the breast: sensitivity of diagnostic techniques and correlation with histopathology.

OBJECTIVE: Our objective was to assess our experience in diagnosing pure tubular carcinoma of the breast and to correlate the radiologic and histopathologic features. MATERIALS AND METHODS: A retrospective review of 932 consecutive cases of proven breast cancer diagnosed between 1990 and 1997 revealed 78 cases (8.4%) of tubular carcinoma in 69 patients. Clinical, imaging, cytologic, and histologic findings were analyzed. RESULTS: Mammography revealed tubular carcinoma in 68 (87%) of the 78 cases. Sonography showed tubular carcinoma in all 38 cases in which it was used; nine of these lesions were mammographically occult. These nine lesions were slightly, but not significantly (p < .05), smaller than the 29 lesions that had also been detected on mammography. Large core needle biopsy was performed in 22 patients (sensitivity, 91%). At biopsy, diagnoses were malignant (n = 16 [73%]), suspicious (n = 4 [18%]), atypia (n = 1 [4.5%]), and benign (n = 1 [4.5%]). Fine-needle aspiration biopsy was used to evaluate 36 cases of tubular carcinoma (sensitivity, 50%); cytologic diagnoses were malignant (n = 15 [42%]), suspicious (n = 3 [8%]), atypia (n = 10 [28%]), and benign (n = 8 [22%]). Only 15 (19%) of the 78 tubular carcinomas were palpable. Other tumors were detected within the excised tissue in 47 of the patients (68%); of these other types of lesions, ductal carcinoma in situ was found most often. CONCLUSION: Most cases of tubular carcinoma can be revealed by mammography; for mammographically occult tubular carcinoma, sonography can be performed. The rate of accuracy for determining the presence of tubular carcinoma is higher with large core needle biopsy than with fine-needle aspiration biopsy. Finally, when tubular carcinoma is diagnosed, other histologic types of carcinoma often occur in the same breast.

BRCA-associated breast cancer: absence of a characteristic immunophenotype.

To characterize the biological features of breast cancer associated with germ-line mutations in BRCA1 and BRCA2, invasive tumors were studied from 58 Jewish women ascertained through studies of early-onset breast cancer. All women were tested for the BRCA1 founder mutations 187delAG (commonly known as 185delAG) and 5385insC (commonly known as 5382insC) and the BRCA2 founder mutation 6174delT. Mutations were detected in 17 of 58 (29.3%) women. Comparing BRCA-associated breast cancers (BABCs) to cases arising in women without founder mutations, no differences were noted in tumor size, tumor stage, or frequency of axillary nodal involvement. Infiltrating ductal carcinoma was the predominant histological type in both groups. BABCs were significantly more likely to be of histological grade III (100 versus 63%; P = 0.04), estrogen receptor negative (75 versus 35%; P = 0.004), and HER2/neu negative (87 versus 58%; P = 0.04). An associated intraductal component was present in 59% of BABCs and 76% of cancers not associated with mutations (P = not significant). A high Ki-67 labeling index was more commonly observed in BABCs than in cases without mutations (83 versus 48%; P = 0.09). There were no differences between the two groups in the frequency of expression of epidermal growth factor receptor, cathepsin D, bcl-2, p27, p53, or cyclin D. There were no significant differences in relapse-free or overall survival. These observations suggest that breast cancers arising in Jewish women with germ-line BRCA founder mutations have a greater proliferative potential than cancers in women without such mutations. Additional studies of BABC are required to determine the nature and implications of additional genetic abnormalities occurring in these tumors.

BRCA-associated breast cancer in young women.

PURPOSE: To delineate the clinical characteristics and outcomes of breast cancer that arises in the setting of a germline BRCA mutation and to compare BRCA-associated breast cancers (BABC) with those that arise in women without mutations. PATIENTS AND METHODS: We reviewed the clinical records of 91 Ashkenazi Jewish women ascertained during studies of the genetics of early-onset breast cancer. All women underwent testing for the BRCA1 mutations 185delAG and 5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2 mutation 6174delT. RESULTS: Mutations were identified in 30 women (33%). BABC were less likely to present with stage I disease than cases in women without mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%), and more likely to have extensive axillary involvement (25% v 17%). These differences were not statistically significant. BABC were significantly more likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor-negative (70% v 34%, P=.04). In the entire cohort, there were no significant differences between BABC and non-BRCA-associated cancers in 5-year relapse-free survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v 68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2 years of study entry, there was a trend toward shorter event-free survival in BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA mutations were significantly more likely to develop contralateral breast cancer at 5 years (31% v 4%, P=.0007). CONCLUSION: BABC present with adverse clinical and histopathologic features when compared with cases not associated with BRCA mutations. However, the prognosis of BABC appears to be similar to that of nonassociated cancer. Further studies of incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.

Surgical treatment and lymphedema.

BACKGROUND: Lymphedema is a serious and disabling complication of the treatment of breast carcinoma. This is related directly to the removal of axillary lymph nodes. Because lymph node status is the single most important predictor of outcome, it is necessary to obtain accurate information. Whereas breast conservation has become the preferred approach for treating early breast carcinoma, the accompanying axillary dissection continues to cause morbidity. METHODS: The history of the operations for breast carcinoma is reviewed, and the anatomy, techniques, and complications of axillary lymphadenectomy are described. Data to support the necessity for accurate axillary staging is presented, and results of noninvasive axillary staging approaches are discussed. The technique and value of sentinel node biopsy are presented. RESULTS: Axillary lymphadenectomy is required where lymph node metastases are present to accomplish local control, improve survival, and provide information for staging to plan adjunctive therapy. Noninvasive techniques do not yet provide high enough sensitivity to assess the status of the axilla. The sentinel lymph node biopsy is a technique that can identify those patients who require axillary lymphadenectomy. CONCLUSIONS: Screening mammography has been responsible for down-staging the size of detected breast carcinomas, so that the axillary dissection may be omitted in small carcinomas of favorable histologic type. For carcinomas in which the probability of axillary metastases exists, by using the sentinel lymph node biopsy, axillary dissections can be avoided when results are negative, and the risk of lymphedema can be reduced.

American Cancer Society guidelines for the early detection of breast cancer: update 1997.

The American Cancer Society (ACS) convened a workshop in March 1997 to consider new scientific findings related to breast cancer screening and to determine whether these findings warrant a change in the existing ACS guidelines. The meeting was timed so that participants could benefit from new data related to screening women aged 40 to 49 years. A recommendation based on the new data and subsequently approved by the ACS Board of Directors is reported.

Stereotactic fine-needle aspiration biopsy for the evaluation of nonpalpable breast lesions: report of an experience based on 2,988 cases.

BACKGROUND: The increasing use of mammography has led to a significant increase in the detection of clinically occult lesions, the majority of which prove to be benign. SFNB has been suggested as a means of expediting a diagnosis for lesions that are malignant while limiting surgical biopsies for those that are benign. METHODS: Clinically occult mammographic lesions were assessed by SFNB in 2,988 patients. Definitive histologic diagnoses were made on surgical specimens in all instances in which the cytologic diagnosis was malignant, suspicious, or atypical. Patients with benign cytology were either followed with interval mammograms or underwent surgical biopsy. RESULTS: Two hundred ninety-one of the 295 lesions (99%) diagnosed as cancer via SFNB were confirmed by histopathology. Twenty-two of the 22 lesions (100%) that were diagnosed as suspicious were diagnosed on histopathology as malignant. Forty-three of the 70 lesions (61%) with cytologic atypia were diagnosed on histopathology to be malignant. CONCLUSIONS: SFNB is an accurate means of diagnosing carcinoma, but must be followed by surgical biopsy when the cytology shows atypia. For lesions diagnosed as benign by SFNB, close interval mammography is essential.

Mammographically detected breast lesions: clinical importance of cytologic atypia in stereotaxic fine-needle aspiration biopsy samples.

PURPOSE: To correlate cytologic findings of stereotaxic fine-needle aspiration biopsy samples with histologic findings of excised samples of nonpalpable mammographically detected lesions. MATERIALS AND METHODS: In a retrospective review of 2,988 consecutive stereotaxic fine-needle aspiration biopsy samples of nonpalpable breast lesions obtained within 5 years, 70 samples were categorized as atypical. Excision with needle localization and specimen radiography were performed in all lesions; cytologic findings of aspirates were correlated with histologic findings of excised samples. Histologic findings were the standard of reference. RESULTS: Of the 70 atypical aspirates, 27 were benign (38%) and 43 were malignant (61%). Both the benign and the malignant lesions had an average size at mammography of 1.1 cm. The nuclear grade was low in 21 (49%), moderate in 16 (37%), and high in six (14%) of the malignant lesions. There were axillary lymph node metastases in four samples (9%). CONCLUSION: Although lesions with atypical aspirates usually are benign, to achieve a low prevalence of false-negative diagnoses atypia must be interpreted as potential malignancy.

Breast cancer after breast augmentation with silicone implants.

BACKGROUND: Although epidemiological studies have failed to demonstrate an increased incidence of breast cancer in women who had undergone prior prosthetic augmentation mammoplasty (PAM), it has been reported that when breast cancer arises in this group it presents mostly in a palpable form and at a more advanced stage. This is thought to be secondary to suboptimal mammographic evaluation caused by the masking effect of the implant. This study was undertaken to determine, in our experience, whether breast cancer arising in women who had undergone PAM could be detected in a prepalpable form by mammography and whether it presented at a more advanced stage as compared with nonaugmented women with breast cancer. METHODS: The charts of 22 patients, treated by at least one of the authors, in whom 23 breast cancers developed after PAM (group A) were retrospectively reviewed. The comparison groups consisted of 611 nonaugmented patients who underwent 636 procedures for the treatment of primary breast cancer at our institution (group B) and the surveillance, epidemiology, and end results (SEER) data (group C). Parameters studied were mode of detection, tumor size, axillary lymph node involvement, and histopathology. RESULTS: No significant differences between the groups were found in mean tumor size (group A vs. group B), the incidence of preinvasive cancer (group A vs. group B) or axillary lymph node involvement (group A vs. group B and group A vs. group C). Breast-preserving surgery was performed significantly less in augmented patients (group A vs. group B). CONCLUSION: We conclude that prepalpable and preinvasive breast cancer can be detected in the PAM patient by mammography and that the stage of presentation in this group is not significantly different than in nonaugmented patients. Total mastectomy is preferred over breast-preserving procedures for the treatment of breast cancer in the PAM patient.

Stereotactic aspiration biopsy of nonpalpable nodules of the breast.

To evaluate the reliability of stereotactic aspiration biopsy (SAB) in assessing which nonpalpable nodules of the breast should be excised, SAB was performed upon 373 nodules. The nodules were classified as well-circumscribed or irregular and evaluated for the presence of microcalcifications. The cytologic diagnoses were classified as malignant, atypical or benign. Cytologically malignant and atypical nodules were excised. Benign nodules were excised if there was a family or past history of carcinoma of the breast or if they changed mammographically. Twenty-five nodules proved to be malignant. Of these, the diagnoses by stereotactic aspiration biopsy were adenocarcinoma in 20 patients, atypical in three, malignant hemangiopericytoma in one patient and benign in one. The borders of the malignant nodules were well-defined in eight patients and irregular in 17. Three malignant nodules with irregular borders had clustered microcalcifications. One false-positive instance was a sclerosing papilloma with atypical hyperplasia. Twenty-four nodules with benign cytologic diagnoses, which were excised, proved to be benign. An additional 132 nodules with benign cytologic diagnoses had six month interval mammograms for two years; 131 were without interval change and one increased in size and proved to be a carcinoma. SAB is reliable for diagnosing nonpalpable nodules. Nodules with malignant and atypical results must be excised. It is reasonable to have follow-up evaluation of well-defined nodules mammographically when the aspirate is benign.

Fine needle aspiration biopsy in patients with augmentation prostheses and a palpable mass.

Six patients with augmentation prostheses presented with a firm, painless, breast mass that could not be visualized by mammography. One lesion was demonstrated to be solid by ultrasound, and the remaining sonograms were nondiagnostic. The lesions were indistinguishable from carcinoma, by physical examination. All of the patients had fine needle aspiration biopsy despite close proximity to the implant. The patients all had silicone granulomas related to silicone leakage. Our experience suggests that fine needle aspiration biopsy is a useful technique to evaluate palpable breast masses that are not visualized by mammography in patients with augmentation prostheses.

Distinction between postsurgical changes and carcinoma by means of stereotaxic fine-needle aspiration biopsy after reduction mammaplasty.

Stereotaxic fine-needle aspiration biopsy (SFNAB) was performed to evaluate suspicious mammographic findings (31 stellate lesions, 20 regions of grouped calcifications, two nodules, and one area of prominent trabecular markings) in 54 patients who had undergone reduction mammaplasty. SFNAB findings were correlated with findings in histologic specimens whenever possible; the cytologic samples were classified as malignant, atypical, or benign. In 22 lesions, the abnormalities on mammograms were considered highly suspicious for malignancy. In the 32 others, the degree of suspicion was lower, but these lesions had a change in appearance since acquisition of the first postoperative mammogram. SFNAB enabled diagnosis of adenocarcinoma in five women. Patients who have undergone mastectomy with reconstruction of one breast and mammaplasty in the other are at higher risk for development of contralateral breast cancer, as are all patients who have had such cancer. SFNAB is reliable for evaluation of suspicious mammographic abnormalities that develop after mammaplasty and findings that change after acquisition of the first postoperative mammogram.

Breast cancer. Importance of adequate surgical excision prior to radiotherapy in the local control of breast cancer in patients treated conservatively.

The extent of excision performed for mammary carcinoma prior to radiotherapy as a risk factor for local recurrence was studied in 503 patients. Three hundred twenty-three tumors (62%) were excised with a minimal rim of tissue (tumorectomy). One hundred forty-two patients (27%) had wide excision and 56 (11%) had quadrantectomy. Tumor stage, size, and radiation treatment were similar for all groups. Forty-one percent of tumorectomies had involved margins, and only 14% and 7% were involved in the wide excision and quadrantectomy groups, respectively. Local failure was 15% for tumorectomy, 7% for wide excision, and 5% for quadrantectomy. In T1 ductal carcinoma, only 4% of those with excisions greater than 5 cm had recurrences. Lesser excision had 20% recurrence. Extent of excision before radiotherapy is an important risk factor for recurrence. Failure was inversely proportional to the amount of breast tissue resected. Narrow excision should be discouraged since a larger tumor burden remains that may not be sterilized by radiation.