Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.

BACKGROUND: To the authors' knowledge, there are no long-term cohort studies of lymphedema, despite the substantial morbidity of arm swelling. The goal of this study was to identify prevalence of breast carcinoma-related lymphedema, time of onset, and associated predictive factors. METHODS: A cohort of 923 women consecutively treated with mastectomy and complete axillary dissection at our center between 1976 and 1978 was observed intensively for 20 years. Two hundred sixty-three study subjects (28.5%) who were alive and recurrence free constituted the cohort for the current study. A subset of 52 women (20% of study population) with contralateral mastectomy was analyzed separately. Subjects reported circumferential arm measurements taken using a validated instrument. In addition to providing analysis of clinical and treatment variables, this study is the first to the authors' knowledge to analyze possible etiologic factors in the posttreatment years, such as occupation, general physical activity, and sports/leisure activities. Univariate and multivariate analytic methods were used. RESULTS: At 20 years after treatment, 49% (128 of 263) reported the sensation of lymphedema. Arm swelling measurements were severe (> or = 2.0 in [5.08 cm]; patients reported measurement in inches) for 13% (33 of 263 women). Seventy-seven percent (98 of 128) noted onset within 3 years after the operation; the remaining percentage developed arm swelling at a rate of almost 1% per year. Of the 15 potential predictive factors analyzed, only 2 were statistically significantly associated with lymphedema: arm infection/injury and weight gain since operation (P < 0.001 and P = 0.02, respectively). CONCLUSIONS: This defined cohort, treated by axillary dissection 20 years ago, documents the high prevalence of lymphedema and its time course. Two significantly associated factors, both potentially controllable, are identified. The current study provides further support for treatments that limit lymph node dissection. The authors are prospectively evaluating patients undergoing sentinel lymph node biopsy.

Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma.

BACKGROUND: The combined approach of radioactive tracer and blue-dye mapping of sentinel lymph nodes (SLN) has evolved into a safe and effective alternative to routine axillary node dissection in specific patient populations with breast carcinoma. The optimal route of injection for the isotope has not been clearly defined. To assess the intradermal route of isotope injection, we prospectively evaluated 100 patients with biopsy-proven invasive breast carcinoma with SLN biopsy followed by planned axillary node dissection. METHODS: All patients were given an intradermal injection of Tc-99m sulfur colloid and an intraparenchymal injection of blue dye. All patients underwent a complete axillary node dissection. Each sentinel node was serially sectioned and examined by immunohistochemistry. RESULTS: Sentinel nodes were successfully identified in 99% of cases. Forty-six patients had axillary metastases; of these, four had falsely negative sentinel nodes (false-negative rate, 9%). The false-negative rate was 0 of 24 (0%) for T1 tumors, 2 of 18 (11%) for T2 tumors, and 2 of 4 (50%) for T3 tumors. Three of four patients with false negatives had palpable, clinically suspicious axillary nodes found intraoperatively. If these cases are excluded, the accuracy of the procedure was 100% for T1 and T2 tumors. Of the 42 positive axillae identified by SLNB (true positives), 40 were localized using the intradermal injection of radioisotope; in 13 of these cases, this was the only method that identified the true-positive node. CONCLUSION: These data demonstrate that intradermal injection of radioactive tracer is an effective method of localizing the SLN in cases involving small breast cancers. Further investigation is warranted before this technique is adopted for use in larger breast cancers. Intraoperative examination and biopsy of any suspicious nonsentinel nodes are critical.

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.

Sentinel lymph node biopsy: is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?

BACKGROUND: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to determine the incidence of sentinel node metastases in patients with high-risk ductal carcinoma-in-situ (DCIS) and DCIS with microinvasion (DCISM). METHODS: From November 1997 to November 1999, all patients who underwent sentinel node biopsy for high-risk DCIS (n = 76) or DCISM (n = 31) were enrolled prospectively in our database. Patients with DCIS were considered high risk and were selected for sentinel lymph node biopsy if there was concern that an invasive component would be identified in the specimen obtained during the definitive surgery. Patients underwent intraoperative mapping that used both blue dye and radionuclide. Excised sentinel nodes were serially sectioned and were examined by hematoxylin and eosin and by immunohistochemistry. RESULTS: Of 76 patients with high-risk DCIS, 9 (12%) had positive sentinel nodes; 7 of 9 patients were positive for micrometastases only. Of 31 patients with DCISM, 3 (10%) had positive sentinel nodes. 2 of 3 were positive for micrometastases only. Six of nine patients with DCIS and three of three with DCISM and positive sentinel nodes had completion axillary dissection; one patient with DCIS had an additional positive node detected by conventional histological analysis. CONCLUSIONS: This study documents a high incidence of lymph node micrometastases as detected by sentinel node biopsy in patients with high-risk DCIS and DCISM. Although the biological significance of breast cancer micrometastases remains unclear at this time, these findings suggest that sentinel node biopsy should be considered in patients with high-risk DCIS and DCISM.

Breast cancer during pregnancy: diagnostic and therapeutic dilemmas.

The management of breast cancer associated with pregnancy encompasses many diagnostic and therapeutic dilemmas. The various modalities used for screening, diagnosis, and staging of breast cancer are not always applicable during pregnancy. The risk to the unborn child plays a major role in the decision process. Overall, the prognosis of patients with pregnancy-associated breast cancer is worse because a large proportion of patients are first seen with more advanced disease. However, stage for stage, the prognosis is similar.

Long term follow-up of women with ductal carcinoma in situ treated with breast-conserving surgery: the effect of age.

BACKGROUND: Although in recent years there has been a dramatic increase in both the incidence of ductal carcinoma in situ (DCIS) and breast-conserving therapy for patients who have this disease, the optimal treatment for these patients remains controversial. Most data regarding outcomes have come from small, retrospective studies, with little data published from prospective, randomized studies. This study investigates the effects of age, postoperative breast irradiation, and other factors on local relapse free survival after breast-conserving surgery for women with DCIS in a large, single-institution series. METHODS: A review was performed of all patients with DCIS who underwent breast-conserving surgery at Memorial Sloan-Kettering Cancer Center from 1978 through 1990. Of the 171 cases identified, data on follow-up and radiation therapy were available for 157. All available pathology slides (132 of 157) were rereviewed to determine histologic subtype, nuclear grade, presence of necrosis, and microscopic tumor size. Sixty-five patients (41%) received postoperative radiation therapy; selection criteria evolved over the time period. The median follow-up was 74 months. RESULTS: Factors that were significantly (P< or =0.05) associated with a lower recurrence rate were older age, noncomedo subtype, lower nuclear grade, negative margins, and postoperative radiation therapy. The 6-year actuarial recurrence rate was 9.6% for patients who received postoperative radiation therapy and 20.7% for patients who had excision only (P = 0.05). Comparison of patients of ages > or =70, 40-69, and <40 years revealed a significantly lower risk of recurrence with increasing age. Actuarial 6-year local relapse rates were 10.8%, 14.0%, and 47.2%, respectively (P = 0.047). A benefit from radiation therapy was suggested for each age group. There was no statistically significant correlation between age group and any histologic factor examined. In multivariate analysis, only margin status was statistically significant (P = 0.05). CONCLUSIONS: In addition to margin status, pathologic factors, and the use of radiation therapy, age is another factor that should be considered in assessing the risk of local recurrence after breast-conserving surgery for patients with DCIS.

Breast cancer and pregnancy.

Pregnancy-associated breast cancer has an overall worse prognosis than nonpregnancy-associated breast cancers because a large proportion present with more advanced disease. Stage for stage, however, the prognosis is similar. The various modalities used for screening, diagnosis, and staging of breast cancer are not always applicable during pregnancy. Often, a delay in diagnosis may contribute to a more advanced stage at presentation. The management of pregnant women with breast cancer is also different because it involves assessing the possible risks to the fetus versus the maternal benefits.

External compression dressing versus standard dressing after axillary lymphadenectomy.

BACKGROUND: Closed-catheter drainage after axillary lymph node dissection (ALND) for breast cancer may constitute a significant inconvenience to the recovering patient, and may also serve as portals of entry for bacteria. Any intervention that could reduce the volume and duration of postoperative drainage would be beneficial. The purpose of this study was to determine whether an external compression dressing after ALND would decrease postoperative drainage, afford earlier drain removal, and reduce subsequent seroma formation. PATIENTS AND METHODS: One hundred thirty-five women undergoing definitive surgical treatment for breast cancer were randomized to receive a compression dressing (n = 66) or standard dressing (n = 69). They were also stratified for modified radical mastectomy (MRM; n = 74) or breast conservation therapy (BCT; n = 61). All patients had ALND. The compression dressing consisted of a circumferential chest wrap of two 6-inch Ace bandages, held in place by circumferential Elastoplast bandage, and it was applied by the same nurse. This dressing remained intact until postoperative day 4. Patients in the standard dressing group (control) were fitted with a front-fastening Surgibra only. Drains were removed when the total daily amount was <50 cc. Postoperative drainage volume, total days with drain, and frequency of seroma formation were recorded for each patient. RESULTS: After 4 days, wound drainage in both groups was nearly identical (compression = 490 cc, standard = 517 cc; P = 0.48). Total days with drain were also similar (compression = 6.4 days, standard = 6.1 days; P = 0.69). The compression dressing did not reduce seroma formation. In fact, there was a statistically significant increase in the number of seroma aspirations per patient in the compression group (compression = 2.9, standard = 1.8; P <0.01). The increase in seroma aspirations was more significant in MRM patients (compression = 3.1, standard = 1.7; P <0.01) than in BCT patients (compression = 2.6, standard = 1.8; P = 0.20). CONCLUSIONS: External compression dressing fails to decrease postoperative drainage and may increase the incidence of seroma formation after drain removal. Thus, routine use of a compression dressing to reduce postoperative drainage after ALND for breast cancer is not warranted.

Immediate reconstruction after complete skin-sparing mastectomy with autologous tissue.

BACKGROUND: Immediate breast reconstruction with autologous tissue can re-create a breast mound that closely resembles the native breast in shape and consistency. Results are limited by scarring and color differences between flap and native breast skin. This study reviews all patients undergoing complete skin-sparing mastectomy with immediate autologous tissue reconstruction over the past 4 years. STUDY DESIGN: Twenty-eight patients with a mean age of 43 years (range, 32-53 years) were retrospectively reviewed. Requirements for the complete skin-sparing approach included a favorable biopsy scar location, adequate areolar diameter, and suitable donor site for autologous tissue reconstruction. Ninety-two percent of patients were reconstructed with a transverse rectus abdominis musculocutaneous flap. RESULTS: There were no instances of flap loss or local recurrence during the followup period (mean, 27 months; range, 14-48 months). Complications at the reconstruction site were minor and limited to cellulitis, periareolar skin loss, and the need for repeat skin excision because of a very close pathologic margin. Donor site complications were seen in five patients. Aesthetic results were judged as excellent or good in 75% of patients. CONCLUSIONS: Complete skin-sparing mastectomy with immediate autologous tissue reconstruction has enhanced immediate breast reconstruction by reducing scar burden and eliminating color differences without an increased incidence of local recurrence. This procedure is limited by appropriate patient selection and technical expertise in performing the mastectomy.

Incidence of breast carcinoma-related lymphedema.

BACKGROUND: Of the 2 million breast carcinoma survivors, perhaps 15-20% are living currently with posttreatment lymphedema. Along with the physical discomfort and disfigurement, patients with lymphedema also must cope with the distress derived from these symptoms. METHODS: To review the medical literature for the question of lymphedema incidence, a comprehensive, computerized search was performed. All publications with subject headings designating breast carcinoma-related lymphedema from 1970 to the present (116 reports) were found, and each summary or abstract was read. Of the 116 reports, 35 discussed the incidence of lymphedema. Of these, seven reports since 1990 from five countries with the most relevance to current patients were then chosen for greater analysis and comparison. RESULTS: The incidence of lymphedema ranged from 6% to 30%. The source of patients, length of follow-up, measurement techniques, and definition of lymphedema varied from report to report. In general, reports with shorter follow-up reported lower incidences of lymphedema. CONCLUSIONS: The definitive study to determine the incidence of lymphedema has not been performed to date. There has been no prospective study in which patients have been followed at intervals with accurate measurement techniques over the long term.

Fatty acid composition of adipose tissue, an indication of dietary fatty acids, and breast cancer prognosis.

PURPOSE: Fatty acid composition of adipose tissue is an indicator of the long-term ingestion pattern of several specific fatty acids. There is good correlation of antecedent diet with the essential fatty acids, and there is reflection of the diet with the fatty acids that can be synthesized. The relationship between the fatty acid levels and lymph node status and clinical outcome was examined. METHODS: At the time of diagnostic surgery, 161 women with clinical stage T1NO breast cancer had subcutaneous adipose tissue (breast and abdominal) aspirated. The concentrations of 35 fatty acids, seven summed classes, and six fatty acid groups were measured by capillary gas chromatography. Lymph node status was determined with axillary dissection, and patients were followed-up (mean, 7.3 years) for clinical outcome. RESULTS: There was no significant association of any adipose tissue fatty acids with overall survival, although few (16 of 161 women) died of breast cancer. However, the odds of having positive lymph nodes (57 of 161 women) were significantly higher for women with a greater adipose tissue proportion of oleic acid (odds ratio [OR], 7.56; 95% confidence interval [CI], 1.78 to 32.1) or total saturated acids (OR, 8.43; 95% CI, 1.48 to 40.0) and significantly lower with a higher proportion of trans fatty acids (OR, 0.24; 95% CI, 0.07 to 0.77), as assessed by multivariate logistic regression. CONCLUSION: These data support previous research with dietary questionnaire methodology, suggesting that specific dietary fatty acids may be associated with breast cancer promotion. Further research with long-term clinical follow-up is necessary to investigate these observations in large, diverse populations before dietary recommendations can be envisioned.

Childbearing issues in breast carcinoma survivors.

BACKGROUND: The issue of the subsequent pregnancy after breast carcinoma treatment is of paramount importance to young survivors and their oncologists. Matters related to having children, whether biologic or not, are analyzed. METHODS: Available evidence on the role of estrogen in the carcinogenesis and promotion of breast carcinoma is summarized. The scanty literature on pregnancy in breast carcinoma survivors is reviewed and evaluated. With reference to infertility as the result of adjuvant treatment, studies on therapy-induced amenorrhea are cited. RESULTS: The survival of women with breast carcinoma is not decreased by subsequent pregnancy in any of the published series. Nevertheless, several biases may be present, making the results less than conclusive; no prospective studies exist. Theoretic concern of tumor promotion may be justified when considering the long term exposure to intense gestational hormones in the presence of established breast carcinoma with possible micrometastases. As a separate issue, the common situation of chemotherapy-induced amenorrhea may not permit pregnancy. Information for the breast carcinoma survivor on assisted conception and adoption is limited. CONCLUSIONS: Further research on the safety of subsequent pregnancy after breast carcinoma treatment is needed; the authors report that they are initiating a multicenter prospective study to address these issues.

Pregnancy influences breast cancer stage at diagnosis in women 30 years of age and younger.

BACKGROUND: To evaluate the purported decreased survival of pregnancy-associated (PA) breast cancer, a previously described homogeneous cohort of women of childbearing age with primary operable cancer was studied. The current analysis was designed to (a) identify those patients among the cohort known to have PA cancer and (b) compare clinical factors, pathologic characteristics, stage at diagnosis, and survival statistics for PA and non-PA cancer subgroups. METHODS: All patients < or =30 years of age who underwent definitive operation between 1950 and 1989 at the Memorial Sloan-Kettering Cancer Center (MSKCC) for primary operable (stages 0-IIIA) breast adenocarcinoma were analyzed. RESULTS: Twenty-two of the 227 young women with primary operable breast cancer had PA cancer. Disease-related survival was decreased (p = 0.004) in these 22 women compared with the remaining 205 patients with non-PA cancer. PA cancer patients were found to have larger tumors (p < 0.005), and a greater proportion had advanced staged (IIB or IIIA) cancers (p < 0.02). Among patients diagnosed with early invasive cancers (stages I or IIA), no difference (p = NS) in survival was observed comparing PA and non-PA subgroups (73% vs. 74% 10-year survival). Patients with stage IIIA cancer had shorter disease-free and overall survival when associated with pregnancy (0% vs. 35% 10-year survival). CONCLUSIONS: Women 30 years of age or younger with PA breast cancer have decreased survival compared with patients with non-PA cancer from the same cohort. Women with PA cancer have larger, more advanced cancers at the time of definitive surgery. Women with early staged PA cancers appear to have survival similar to that for women with early staged non-PA cancer.

The impact of the sequence of radiation and chemotherapy on local control after breast-conserving surgery.

PURPOSE: We conducted this study to evaluate the effects of delaying primary radiation after adjuvant chemotherapy on local control following breast-conserving surgery compared with radiation delivered immediately following surgery. PATIENTS AND METHODS: This retrospective, nonrandomized study evaluated local control in 471 patients treated with breast-conserving surgery and radiation from 1980 through 1990. Three patient subsets were studied, identified by the sequence of radiation and adjuvant therapy if given. The three subgroups were: surgery, radiation, no chemohormonal therapy (332 patients; RT only); surgery, all chemotherapy, radiation (53 patients; chemo first); and surgery, chemotherapy, radiation, chemotherapy (86 patients; sandwich). Median follow-up times ranged from 53 months in the chemo first group to 77 months in the RT only group. RESULTS: All three groups had similar local control rates at 3 and 5 years. At 36 months, the actuarial local control rate achieved by the RT only group was 98% (confidence interval: 95%-99%); by the chemo first group, 94% (CI: 82%-98%); and the sandwich group, 96% (CI: 89%-99%). At 60 months, the local control rate for the RT only group was 96% (CI: 93%-98%), the chemo first group, 86% (CI: 70%-94%) and the sandwich group 95% (CI: 87%-98%). CONCLUSIONS: This report demonstrates no significant difference in the local recurrence rate following breast-conserving surgery and radiation therapy, whether radiation immediately followed the surgery or whether it was delayed by the administration of postsurgical adjuvant chemotherapy. These data differ from other reports, and suggest that this question remains open, requiring further follow-up that focuses not only on local control as an endpoint, but disease-free and overall survival as well.

The foremost cancer--revisited.

In 1969, the late Roald M. Grant, MD, then Editor in Chief of CA, wrote an editorial on breast cancer titled "The Foremost Cancer." In this issue, Jeanne A. Petrek, MD, an Associate Attending Surgeon in the Department of Surgery at the Memorial Sloan-Kettering Cancer Center, and Arthur I. Holleb, MD, CA's Editor Emeritus, update Dr. Grant's essay on breast cancer and comment on the articles that appear in this issue.

Breast cancer during pregnancy.

Breast cancer during pregnancy involves a host of psychosocial, ethical, religious, and legal considerations, as well as medical multidisciplinary decisions. Treatment modalities. Breast or chest wall radiation therapy should be avoided because the fetal dose, regardless of the trimester, can cause permanent complications. In the second and third trimester, chemotherapy is associated with intrauterine growth retardation and prematurity in approximately half of the infants; the risk of birth defects is a concern during the first several weeks. Typical anesthetic agents readily reach the fetus but are not known to be teratogenic. Modified radical mastectomy without delay is the best option in pregnant patients with Stage I or II and some Stage III cancer. Although abortion allows full treatment to the mother, it is not known whether the procedure is therapeutic. Early in pregnancy abortion deserves strong consideration. Prognosis. The poor prognosis of pregnancy-associated breast cancer in the past probably is attributable to a combination of initial delay and possibly to the unfavorable biologic characteristics of pregnancy. When pregnant patients are matched stage for stage with control subjects, survival seems equivalent, although pregnant patients have more advanced stage disease.