Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study.

BACKGROUND: The incidence of chemotherapy-induced amenorrhea (CIA) and the time to subsequent menstrual bleeding in premenopausal breast cancer patients treated with current standard chemotherapy regimens was examined. METHODS: Four hundred sixty-six women ages 20 to 45 years at the time of diagnosis of a stage I to III breast cancer were recruited between January 1998 and July 2002. Patients completed monthly bleeding calendars from the time of study recruitment. Updated medical history data were obtained at 6-month intervals. RESULTS: Most women received doxorubicin and cyclophosphamide (AC); doxorubicin, cyclophosphamide, and paclitaxel (ACT); or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Approximately 41% of women experienced an initial 6 months of CIA, and an additional 29% had at least 1 year of CIA. Approximately half of the women with 6 months of CIA and 29% of those with 1 year of CIA resumed bleeding within the subsequent 3 years, usually in the year after their amenorrheic episode. Resumption of bleeding differed significantly by treatment regimen after 6 months of CIA (P = .002; 68% with AC, 57% with ACT, and 23% with CMF), but not after 1 year of CIA (P = .5). Of the 23% of women who experienced an initial 2-year period of CIA, 10% resumed bleeding within the ensuing 3 years after their amenorrheic episode, but none had regular menses. CONCLUSIONS: A considerable proportion of women treated with chemotherapy will experience periods of CIA, but many will resume bleeding. Newer treatment regimens such as ACT appear to have a higher resumption of bleeding compared with CMF. This finding may have implications for choice of anti-estrogen treatment and for future potential pregnancies/fertility.

Is pregnancy after breast cancer safe?

The impact of treatment on subsequent fertility and the safety of childbearing are major complicating factors for young women diagnosed with breast cancer. As national data indicate women are postponing first pregnancy to older ages; therefore, many young patients are seeking clinical guidance regarding the safety of conception and treatment options that may not prevent subsequent pregnancy. Newly developed chemotherapy protocols of brief duration have improved life expectancy enabling some women to consider childbearing. This study was conducted to compare prognosis among breast cancer patients with and without a subsequent pregnancy. Medical record review of female members of a Northern California prepaid health care plan enabled the identification of 107 women with one or more subsequent pregnancies and 344 cases without a pregnancy, who were diagnosed between 1968 and 1995. Sets were matched on age, year and stage at diagnosis, months of survival and recurrence status at conception. Among the matched sets, neither risk of recurrence nor death differed significantly by subsequent pregnancy history during an average 12 years of follow-up (adjusted hazard ratio [HR] recurrence: 1.2 [0.8, 2.0]; adjusted HR death: 1.0 [0.6, 1.9]). Women interested in preserving their fertility and considering pregnancy are a self-selected population; therefore, to reduce potential bias, cases were matched on recurrence status at time of conception. Although the number of cases was limited, subgroup analyzes indicated a small, nonsignificant adverse effect among women who conceived within 12 months of diagnosis. This analysis of carefully matched cases provides reassurance that long-term prognosis was not adversely affected by subsequent pregnancy.

Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study.

PURPOSE: To assess ovarian function using the surrogate of monthly bleeding after breast cancer treatment in premenopausal women. PATIENTS AND METHODS: Five hundred ninety-five US women age 20 to 45 years were accrued from January 1998 to July 2002 within 8 months of diagnosis with stages I to III breast cancer (median follow-up 45 months). Daily bleeding records were obtained prospectively, as well as extensive clinical, demographic, quality of life, and treatment data. Repeated measures logistic regression was used to assess which variables were predictive of monthly bleeding. RESULTS: Significantly different proportions of women had monthly bleeding depending on their age (P < .001), chemotherapy program (P < .001), and time since treatment regimen. In the month after the standard course of doxorubicin and cyclophosphamide (AC), whether or not followed by paclitaxel or docetaxel, approximately 16% had monthly bleeding compared with the cyclophosphamide, methotrexate, fluorouracil (CMF) group, in which 48% bled (P < .001). Following any AC regimen, there was a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period compared with after CMF in which there was no recovery phase and a continual decline in monthly bleeding to approximately 18% of women at study end (P < .001). Tamoxifen use decreased bleeding between months 12 and 24 after chemotherapy with 15% fewer women having bleeding. CONCLUSION: Using daily menstrual bleeding records, it is demonstrated that age, the specific chemotherapy regimen received, and tamoxifen use impact ovarian function.

The risk of axillary relapse after sentinel lymph node biopsy for breast cancer is comparable with that of axillary lymph node dissection: a follow-up study of 4008 procedures.

OBJECTIVE: We sought to identify the rate of axillary recurrence after sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: SLN biopsy is a new standard of care for axillary lymph node staging in breast cancer. Nevertheless, most validated series of SLN biopsy confirm that the SLN is falsely negative in 5-10% of node-positive cases, and few studies report the rate of axillary local recurrence (LR) for that subset of patients staged by SLN biopsy alone. METHODS: Through December of 2002, 4008 consecutive SLN biopsy procedures were performed at Memorial Sloan-Kettering Cancer Center for unilateral invasive breast cancer. Patients were categorized in 4 groups: SLN-negative with axillary lymph node dissection (ALND; n = 326), SLN-negative without ALND (n = 2340), SLN-positive with ALND (n = 1132), and SLN-positive without ALND (n = 210). Clinical and pathologic characteristics and follow-up data for each of the 4 cohorts were evaluated with emphasis on patterns of axillary LR. RESULTS: With a median follow-up of 31 months (range, 1-75), axillary LR occurred in 10/4008 (0.25%) patients overall. In 3 cases (0.07%) the axillary LR was the first site of treatment failure, in 4 (0.1%) it was coincident with breast LR, and in 3 (0.07%) it was coincident with distant metastases. Axillary LR was more frequent among the unconventionally treated SLN-positive/no ALND patients than in the other 3 conventionally treated cohorts (1.4% versus 0.18%, P = 0.013). CONCLUSIONS: Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.

A prospective analysis of the effect of blue-dye volume on sentinel lymph node mapping success and incidence of allergic reaction in patients with breast cancer.

BACKGROUND: This study examined whether the volume of isosulfan blue dye used in sentinel lymph node (SLN) mapping in breast cancer is related to the SLN identification rate or to the incidence of allergic reactions. METHODS: From January 2001 to November 2002, 1728 breast cancer patients underwent 1832 SLN mapping procedures with the combined technique of intraparenchymal blue dye and intradermal radioisotope. Details of each procedure and all allergic reactions were prospectively recorded. Bilateral synchronous SLN procedures were considered as one dye exposure but as two distinct procedures for determining mapping success. Dye-only success was defined as the proportion of cases in which the SLN was identified by blue dye alone. Overall dye success was defined as the proportion of cases in which the SLN was identified by blue dye with or without isotope. RESULTS: When stratified by volume of blue dye, there were no significant differences in dye-only successes, overall dye successes, or mapping failures. Allergic reactions were documented in 31 (1.8%) of 1728 patients. Hypotensive reactions occurred in 3 (.2%) of 1728 patients; 2 (.1%) required pressor support. There was a nonsignificant trend toward fewer allergic reactions with smaller volumes of blue dye. CONCLUSIONS: In combined-technique SLN mapping protocols for breast cancer, using smaller volumes of blue dye may represent a means of optimizing the safety of the procedure without compromising its success.

Breast cancer in pregnant and postpartum women.

Breast cancer is reported to occur in from 1 in 3000 to 1 in 10,000 pregnancies worldwide. In the United States, 10% to 20% of breast cancers occur in women of childbearing age. Diagnosis and treatment of breast cancer during pregnancy present many additional challenges.

The grading of lymphedema in oncology clinical trials.

Lymphedema is a common late toxicity of cancer therapy. This article describes the rationale and process utilized by the Lymphedema Working Group for the revision and expansion of the Common Toxicity Criteria version 2 (CTC v2.0) lymphedema criteria to produce the CTC v3.0 lymphedema criteria. Established clinician-based rating scales and quantitative instruments are reviewed in this article. None of the extant rating scales have been formally validated, nor has their reliability been assessed. Drawbacks of current scales were considered in formulating CTC v3.0 criteria. Most rely exclusively on volume to diagnose and grade lymphedema. This imposes significant clinical limitations, particularly in the assessment of toxicity in oncology clinical trials. Volume-based rating scales are of little value in rating the severity of bilateral limb and nonlimb edema. Problems with nonvolumetric staging systems (eg, CTC v2.0) include insufficient detail to permit useful discrimination of severity among the majority of lymphedema patients. Technologies for objectively quantifying lymphedema have been developed and validated. Although these are briefly reviewed, it is recognized that cost and access issues limit their widespread clinical utility and, as such, were not considered in developing the CTC v3.0 criteria. The CTC v3.0 lymphedema criteria adopted several innovations. Principle among these was the decision to generate separate criteria for volumetric increase, dermal changes, and subcutaneous fibrosis. We anticipate the use of the new CTC v3.0 lymphedema criteria to begin in mid-2003 for grading the key clinical features of this disorder in oncology clinical trials. The purpose of this article is to familiarize the reader with (1) background on the clinical features of lymphedema, (2) information on established lymphedema rating systems, (3) the consensus process and rationale of the Lymphedema Working Group, (4) the new CTC v3.0, and (5) quantitative techniques for assessment of lymphedema.

Lymphedema management.

Lymphedema, defined as the abnormal accumulation of protein rich fluid dysfunction of the lymphatic system, is a common sequela of cancer therapy. The incidence is highest among patients who have undergone resection and irradiation of a lymph node bed. Recently, increased attention has been focused on the modification of anticancer therapies in an effort to minimize lymphatic compromise. Sentinel lymph node biopsy is an example of a surgical procedure developed to preserve lymphatic function. Concurrent with the development of less invasive treatments, the field of lymphedema management has evolved rapidly over the past decade. Combined manual therapy, often referred to as complex decongestive physiotherapy (CDP), has emerged as the standard of care. CDP combines compression bandaging, manual lymphatic drainage (a specialized massage technique), exercise, and skin care with extensive patient education. Case series collectively describing a mean 65% volume reduction in over 10,000 patients attest its efficacy. Pneumatic compression pumps were historically widely used to control lymphedema. Their use as an isolated treatment modality is now rare. Reliance on pumps diminished with the recognition that they may exacerbate truncal and genital lymphedema, as well as injure peripheral lymphatics when applied at high pressures. Many noncompressive approaches, particularly the use of benzopyrone medications and liposuction, continue to be used abroad.

Skin-sparing mastectomy and immediate autologous tissue reconstruction after whole-breast irradiation.

Traditional breast conservation therapy consists of lumpectomy and whole-breast irradiation. Local recurrence after breast conservation is usually managed with salvage mastectomy. Skin-sparing mastectomy and immediate autologous tissue reconstruction is an accepted method of managing primary breast malignancies with exceptional aesthetic results. The purpose of this study was to evaluate this technique in the previously irradiated breast. This study is a retrospective review of all patients undergoing skin-sparing mastectomy and immediate reconstruction with autologous tissue after failed breast conservation therapy between 1995 and 1999. There were 11 patients with a mean age of 45 years (range, 34 to 58 years). Initial lumpectomy was performed for ductal carcinoma in situ in six patients and infiltrating carcinoma (ductal or lobular) in five patients. The interval from lumpectomy to salvage mastectomy ranged from 12 to 169 months (mean, 44 months). Reconstructive techniques included unipedicled transverse rectus abdominis musculocutaneous (TRAM) flap (n = 4), free TRAM flap (n = 4), and latissimus flap with immediate placement of a saline implant (n = 3). Flap survival was 100 percent, and there were no early flap complications. One patient developed partial-thickness mastectomy flap loss (3 x 3 cm), which was managed conservatively. There were no instances of full-thickness mastectomy skin loss. Late complications included capsular contracture (n = 2), fat necrosis (n = 1), and ventral hernia (n = 1). There was one late death from metastatic disease; the remaining patients were without evidence of disease at a mean of 48 months (range, 30 to 75 months). Aesthetic results were judged as excellent (n = 4), good (n = 5), fair (n = 1), and poor (n = 1). These results demonstrate that skin-sparing mastectomy and immediate autologous tissue reconstruction can be safely performed in patients with previous whole-breast irradiation. Clearly, patient selection is paramount with attention to the quality of the irradiated breast skin and the anatomic location of the recurrent disease. In this experience, the best results were seen after TRAM (pedicled or free) flap reconstruction.

Are the axillary lymph nodes treated by standard tangent breast fields?

BACKGROUND AND OBJECTIVES: With the increasing use of sentinel lymph node biopsy, a growing proportion of women with early-stage invasive breast cancer are undergoing breast conserving surgery without a formal axillary lymph node dissection. A frequent question raised is whether the level I-II axillary lymph nodes are treated with standard breast tangent fields. In an attempt to answer this question, surgical clips placed at the time of the level I-II axillary lymph node dissection were used as a surrogate for the location of the nodes and the simulator films for tangent fields of 45 patients were analyzed. METHODS: Study criteria were as follows: five or more clips placed in the axilla, and all clips and the humeral head visualized on the medial tangent film. Clips were scored as "in" or "out" of the tangent field, as defined by the delineator wires. All technical parameters were analyzed to determine whether any reproducible techniques would consistently include all of the clips and, hypothetically, the axillary nodes at levels I and II. RESULTS: All clips were included in the medial tangent breast radiation field in only 38% (17 of 45) of cases. CONCLUSIONS: The standard, two-field tangent breast fields do not reliably encompass the all level I-II axillary lymph nodes as defined by this study, but some of the nodes were treated in all 45 cases.

Sensory morbidity after sentinel lymph node biopsy and axillary dissection: a prospective study of 233 women.

BACKGROUND: We prospectively compared the sensory morbidity and lymphedema experienced after sentinel node biopsy (SLNB) and axillary dissection (ALND) over a 12-month period by using a validated instrument. METHODS: Patients undergoing breast-conserving therapy completed the Breast Sensation Assessment Scale (BSAS) at baseline and 3, 6, and 12 months after surgery. Repeated-measures analysis of variance was used to compare ALND and SLNB over the 12-month period. Upper- and lower-arm circumference measurements at baseline and 12 months were used to assess lymphedema. RESULTS: SLNB was associated with substantial sensory morbidity, although significantly less than ALND, over time on all four subscales and the summary score. A statistically significant improvement in sensory morbidity occurred for both groups in the first 3 months, with no further change thereafter. For both types of axillary surgery, younger patients had significantly higher BSAS scores than older patients. There was no significant difference in arm circumference between patients with SLNB and ALND at 12 months. CONCLUSIONS: Among women undergoing breast-conserving therapy, SLNB has significant sensory morbidity, although approximately half that of ALND. Sensory morbidity improves in the first 3 months after surgery, but patients continue to report sensory morbidity at 1 year. Longitudinal follow-up is required to further assess lymphedema.

Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a new standard of care for axillary node staging in patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 10% to 15% will develop local relapse requiring reoperation. Although previous breast or axillary surgery is often considered a contraindication to SLN biopsy, few data support this position. We report our experience with SLN biopsy in the reoperative setting. STUDY DESIGN: We examined the 3,490 consecutive SLN biopsy procedures for breast cancer performed at our institution between September 1996 and July 2001; 32 (1%) of these followed previous axillary surgery: 22 (69%) for breast recurrence after SLN biopsy or axillary lymph node dissection (ALND); 7 (22%) after a recent, failed SLN biopsy or inadequate ALND; and 3 (9%) after earlier axillary surgery for an unrelated condition. RESULTS: SLNs were identified in 24 of 32 (75%) cases and were positive in 3 of 24 (13%). Reoperative SLN biopsy was more successful when less than 10 versus 10 or more nodes had been removed previously (87% versus 44%). Both blue dye and isotope identified the SLN in 16 of 24 successful procedures (67%). Additional, nonsentinel nodes (mean, eight nodes) were removed in 17 of 24 patients (71%) and were negative in all cases. At a median followup of 13 months, no axillary recurrences have occurred. CONCLUSIONS: Reoperative SLN biopsy after earlier SLN biopsy or ALND is feasible in selected breast cancer patients and is more likely to succeed when fewer than 10 nodes were removed during the earlier procedure. Further study is required to better define the subset of patients in whom reoperative SLN biopsy can replace ALND.

Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer.

UNLABELLED: In the United States, identification of the sentinel lymph node (SLN) requires the use of (99m)Tc-labeled colloid, 1% isosulfan blue dye, or both to trace the lymphatic drainage of a given neoplasm. We report our experience with adverse reactions to isosulfan blue dye during SLN mapping in breast cancer. A chart review of the breast cancer SLN database was performed; it included 2392 sequential patients who underwent SLN biopsy involving isosulfan blue dye at Memorial Sloan-Kettering Cancer Center from September 12, 1996, to August 17, 2000. Thirty-nine of 2392 patients (1.6%) had a documented allergic reaction during the mapping procedure. Most reactions (69%) produced urticaria, blue hives, a generalized rash, or pruritus. The incidence of hypotensive reactions was 0.5%. Although anaphylaxis after the injection of isosulfan blue dye is rare, this article highlights the need to suspect anaphylaxis when hemodynamic instability occurs after the injection of this compound. Our experience indicates that bronchospasm and respiratory compromise are unusual and that most patients do not require emergent intubation and can be managed with short-term pressor support. In addition, our data indicate that patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye. IMPLICATIONS: We report the largest single-institution review of adverse reactions to injection of isosulfan blue dye during sentinel lymph node mapping in breast cancer. Bronchospasm and respiratory compromise are unusual, and most patients can be treated with short-term pressor support. Patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye.