Pharmacokinetics and tolerability of exemestane in combination with raloxifene in postmenopausal women with a history of breast cancer.

PURPOSE: Raloxifene is a second-generation selective estrogen receptor modulator that reduces the incidence of breast cancer in postmenopausal women. Exemestane, a steroidal aromatase inhibitor, decreases contralateral new breast cancers in postmenopausal women when taken in the adjuvant setting. Preclinical evidence suggests a rationale for coadministration of these agents to achieve complete estrogen blockade. EXPERIMENTAL DESIGN: We tested the safety and tolerability of combination exemestane and raloxifene in 11 postmenopausal women with a history of hormone receptor-negative breast cancer. Patients were randomized to either raloxifene (60 mg PO daily) or exemestane (25 mg PO daily) for 2 weeks. Patients then initiated combination therapy at the same dose levels for a minimum of 1 year. Pharmacokinetic and pharmacodynamic data for plasma estrogens, raloxifene, exemestane, and their metabolites were collected at the end of single-agent therapy and during combination therapy. RESULTS: Plasma concentration-time profiles for each drug were unchanged with monotherapy versus combination therapy. Raloxifene did not affect plasma estrogen levels. Plasma estrogen concentrations were suppressed below the lower limit of detection by exemestane as monotherapy and when administered in combination with raloxifene. The most common adverse events of any grade included arthralgias, hot flashes, vaginal dryness and myalgias. CONCLUSIONS: In this small study, coadministration of raloxifene and exemestane did not affect the pharmacokinetics or pharmacodynamics of either agent to a significant degree in postmenopausal women. The combination of estrogen receptor blockade and suppression of estrogen synthesis is well tolerated and warrants further investigation.

Magnetic resonance imaging detects unsuspected disease in patients with invasive lobular cancer.

BACKGROUND: Predicting the extent of disease in the breasts of patients with invasive lobular cancer (ILC) can be difficult because of the limits of physical examination and standard imaging. We determined the utility of magnetic resonance imaging (MRI) in finding otherwise unsuspected cancer in the ipsilateral or contralateral breast of patients with ILC. METHODS: Through database review of all breast MRIs performed between January 1, 1999, and December 30, 2002, we identified patients with newly diagnosed ILC who underwent an MRI for extent-of-disease evaluation or contralateral screening. MRI findings separate from the primary tumor were biopsied and correlated with pathology by using MRI-guided biopsy. RESULTS: Sixty-two patients were identified. In all, 59 ipsilateral and 57 contralateral studies were performed. Suspicious lesions separate from the primary tumor were found by MRI in 38 (61%) of 62 patients. Eight patients were excluded from further analysis (seven elected mastectomy without biopsy; one had an unguided excision). Nineteen of 51 patients with an ipsilateral finding underwent MRI-guided biopsy, which revealed cancer in 11, or 22% of those imaged. Twenty of 53 patients with a contralateral finding underwent MRI-guided biopsy, which revealed cancer in 5, or 9% of those imaged. CONCLUSIONS: MRI of the breast identifies unsuspected multicentric or contralateral cancer in patients with ILC. These findings support the use of MRI in selected patients with ILC, particularly in the ipsilateral breast.

A trend analysis of the relative value of blue dye and isotope localization in 2,000 consecutive cases of sentinel node biopsy for breast cancer.

BACKGROUND: Among the advocates of blue dye, isotope, or combined dye-isotope mapping of the sentinel lymph node (SLN) for breast cancer, there is no universal consensus as to which technique is optimal and whether the relative value of each method changes with increasing experience. The objective of this study was to examine the relative contributions of blue dye and radioisotope to successful identification of the SLN as the SLN-mapping technique evolved over our first 2,000 consecutive cases. STUDY DESIGN: Using the first 2,000 consecutive SLN biopsy procedures for breast cancer, performed by eight surgeons (none previously experienced in SLN techniques) at one institution, using a combined technique of blue dye and isotope mapping, we report the institutional learning curve and the relative contributions of dye and isotope to identifying both the SLN and the positive SLN, by increments of 500 cases. RESULTS: Comparing the first 500 with the most recent 500 cases, success in identifying the SLN by blue dye did not improve with experience, although success in isotope localization steadily increased, from 86% to 94% (p < 0.00005). With the increasing success of isotope mapping, the marginal benefit of blue dye (the proportion of cases in which the SLN was identified by blue dye alone) steadily declined, from 9% to 3% (p = 0.0001). Parallel to this trend, the proportion of positive SLNs identified by blue dye did not change with experience (89% to 90%), but isotope success steadily increased, from 88% to 98% (p = 0.0015). The proportion of positive SLNs identified by blue dye alone declined from 12% to 2% (p = 0.0015). CONCLUSIONS: Using a combined technique of blue dye and radioisotope mapping, and with refinement of the radioisotope technique, we report 97% success identifying the SLN. Although we continue to recommend the use of both methods in SLN mapping for breast cancer, we observe with experience a declining marginal benefit for blue dye.

Insurance reimbursement for risk-reducing mastectomy and oophorectomy in women with BRCA1 or BRCA2 mutations.

PURPOSE: Risk-reducing surgery is an important option for women with BRCA1 and BRCA2 mutations. There are reports in the literature that insurance reimbursement for these procedures varies greatly. Because health insurance coverage significantly affects medical decision-making, current information regarding reimbursement practices of third-party payers is needed. METHODS: Retrospective study of hospital billing records of 38 women with documented BRCA1 or BRCA2 mutations who underwent either a risk-reducing mastectomy or a risk-reducing oophorectomy between March 1, 1997, and July 30, 2000. RESULTS: Complete billing and reimbursement information was available for 35 women undergoing a total of 39 risk-reducing surgeries. A total of 38 of 39 (97%) risk-reducing surgeries were covered in full, less applicable coinsurance and deductibles. The rate of insurance reimbursement did not vary with type of insurance, personal history of cancer, or type of procedure. CONCLUSION: Insurance carriers reimbursed the vast majority of BRCA mutation carriers undergoing risk-reducing surgery.

Intradermal isotope injection is superior to intramammary in sentinel node biopsy for breast cancer.

BACKGROUND: The optimal sentinel lymph node (SLN) biopsy technique remains undefined in breast cancer. Injecting radiotracer or blue dye by a variety of routes seems to stage the axilla with comparable accuracy, and we have hypothesized that the dermal and the parenchymal lymphatics of the breast drain to the same SLN in most patients. Two previous studies from our institution support this concept: (1) a single-surgeon series of 200 consecutive SLN biopsy procedures demonstrating a high dye-isotope concordance for both intradermal (ID) and intraparenchymal (IP) isotope injection, and (2) a series of 100 procedures validated by a backup axillary dissection (ALND) in which the false-negative rate following ID isotope injection was comparable to that of our previous results with IP injection. Here, we directly compare the results of SLN biopsy using either ID or IP isotope injection for our entire experience of SLN biopsy procedures in which a backup ALND was done. METHODS: This is a retrospective, nonrandomized study of 298 clinical stage I to II breast cancer patients having SLN biopsy with a backup ALND planned in advance, comparing the results of ID (n = 164) and IP (n = 134) isotope injection. All patients had IP injection of blue dye. Endpoints included (1) successful SLN identification, (2) false-negative rate, (3) dye-isotope concordance, and (4) the SLN/axillary background isotope count ratio. RESULTS: ID isotope was more successful than IP, identifying the SLN in 98% versus 89% of cases, respectively. False-negative results (4.8% vs 4.4%) and dye-isotope concordance (92% vs 93%) were comparable between the 2 groups, and SLN/axillary background isotope count ratios were significantly higher with ID than with IP injection (288/1 vs 59/1). CONCLUSIONS: ID isotope injection identifies the SLN more often than IP, stages the axilla with comparable accuracy, and is associated with higher levels of SLN isotope uptake. The dermal and parenchymal lymphatics of the breast drain to the same axillary SLN in most breast cancer patients, and ID isotope injection is the procedure of choice in this setting.

Patient reluctance toward tamoxifen use for breast cancer primary prevention.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial demonstrated that tamoxifen reduces the incidence of new breast cancers by 49% in women at increased risk for breast cancer development. Tamoxifen does have side effects, however, including marginally increased risks of endometrial cancer and thromboembolic events. In this study, women at increased risk for breast cancer development were offered tamoxifen. Their knowledge of tamoxifen as a chemopreventive agent was assessed, and factors influencing their acceptance of tamoxifen and willingness to take it were determined. METHODS: Forty-three patients were identified who qualified to take tamoxifen for primary prevention. Patients qualified by having at least a 1.7% 5-year risk of developing breast cancer, the criteria for entry into the NSABP P-1 trial. Patients initially completed questionnaires designed to assess their knowledge of tamoxifen and its associated risks and benefits. Patients were then provided neutral educational sessions and literature delineating the actual risks and benefits of tamoxifen. Subsequently, patients' decisions regarding taking tamoxifen were reassessed. RESULTS: Mean patient age was 52.8 years, with a range of 39 to 74 years. Ten patients (23.2%) qualified based on the presence of lobular carcinoma in situ (LCIS), seven patients (16.3%) qualified based on increased risk secondary to age >60 years, and 26 patients (60.5%) age range 35 to 59 qualified based on risk profiles demonstrating significantly increased risk. Of the total 43 patients, two (4.7%) elected to start taking tamoxifen. Fifteen patients (34.8%) declined immediately, and 26 patients (60.5%) were undecided initially but ultimately declined. Educational sessions did not influence patients' decisions. Fear of side effects, including endometrial cancer, thromboembolic events, and menopausal symptoms, was the most commonly cited reason for declining to take tamoxifen. CONCLUSIONS: In this study, the vast majority of patients at increased risk for breast cancer perceived that the risks of taking tamoxifen outweighed the benefits and declined to take it.

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.

Sentinel lymphadenectomy accurately predicts nodal status in T2 breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has emerged as a reliable, accurate method of staging the axilla for early breast cancer. Although widely accepted for T1 lesions, its use in larger tumors remains controversial. This study was undertaken to define the role of SLNB for T2 breast cancer. STUDY DESIGN: From a prospective breast sentinel lymph node database of 1,627 patients accrued between September 1996 and November 1999, we identified 223 patients with clinical T1-2N0 breast cancer who underwent 224 lymphatic mapping procedures and SLNB followed by a standard axillary lymph node dissection (ALND). Preoperative lymphatic mapping was performed by injection of unfiltered technetium 99 sulfur colloid and isosulfan blue dye. Data about patient and tumor characteristics and the status of the sentinel lymph nodes and the axillary nodes were analyzed. Statistics were performed using Fisher's exact test. RESULTS: Two hundred four of 224 sentinel lymph node mapping procedures (91%) were successful. Median tumor size was 2.0 cm (range 0.2 to 4.8 cm). One hundred forty-five of the 204 patients had T1 lesions and 59 patients had T2 lesions. There were 92 pathologically positive axillae, 5 (5%) of which were not evident either by SLNB or by intraoperative clinical examination. The false-negative rate and accuracy were not significantly different between the two groups, but axillary node metastases were observed more frequently with T2 than with T1 tumors (p = 0.005); other factors, including patient age, prior surgical biopsy, upper-outer quadrant tumor location, and tumor lymphovascular invasion were not associated with a higher incidence of false-negative SLNB in either T1 or T2 tumors. CONCLUSIONS: SLNB is as accurate for T2 tumors as it is for T1 tumors. Because no tumor or patient characteristics predict a high false-negative rate, all patients with T1-2N0 breast cancer should be considered candidates for the procedure. Complete clinical examination of the axilla should be undertaken to avoid missing palpable axillary nodal metastases.

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.

Palpable breast masses: is there a role for percutaneous imaging-guided core biopsy?

OBJECTIVE: The purpose of this study was to evaluate percutaneous imaging-guided core biopsy in the assessment of selected palpable breast masses. MATERIALS AND METHODS: Of 1388 consecutive breast lesions that had percutaneous imaging-guided core biopsy, 155 (11%) were palpable. Palpable masses referred for percutaneous imaging-guided core biopsy included lesions that were small, deep, mobile, vaguely palpable, or multiple. Biopsy guidance was sonography in 140 lesions (90%) and stereotaxis in 15 (10%). Surgical correlation or minimum of 2 years follow-up is available in 115 palpable masses in 107 women. Medical records, imaging studies, and histologic findings were reviewed. RESULTS: Of 115 palpable breast masses, 98 (85%) were referred by surgeons to the radiology department for percutaneous imaging-guided core biopsy and 88 (77%) had percutaneous imaging-guided core biopsy on the day of initial evaluation at our institution. Percutaneous imaging-guided core biopsy spared additional diagnostic tissue sampling in 79 (74%) of 107 women, including 57 women with carcinoma and 22 women with benign findings. Percutaneous imaging-guided core biopsy did not spare additional tissue sampling in 28 women (26%), including 15 women in whom surgical biopsy was recommended on the basis of percutaneous biopsy findings and 13 women with benign (n = 7) or malignant (n = 6) percutaneous biopsy findings who chose to undergo diagnostic surgical biopsy. CONCLUSION: Percutaneous imaging-guided core biopsy is useful in the evaluation of palpable breast masses that are small, deep, mobile, vaguely palpable, or multiple. In this study, percutaneous imaging-guided core biopsy spared additional diagnostic tissue sampling in 74% women with palpable breast masses.

Prone breast radiotherapy in early-stage breast cancer: a preliminary analysis.

PURPOSE: Women with large breasts have marked dose inhomogeneity and often an inferior cosmetic outcome when treated with breast conservation compared to smaller-sized patients. We designed a prone breast board, which both minimizes breast separation and irradiated lung or heart volume. We report feasibility, cosmesis, and preliminary local control and survival for selected women with Stage 0-II breast cancer. MATERIALS AND METHODS: Fifty-six patients with clinical Stage 0-II breast cancer were treated with lumpectomy and breast irradiation utilizing a prototype prone breast board. A total of 59 breasts were treated. Indications for treatment in the prone position were large or pendulous breast size (n = 57), or a history of cardiopulmonary disease (n = 2). The median bra size was 41D (range, 34D-44EE). Cosmesis was evaluated on a 1-10 (worst-to-best) scale. RESULTS: Acute toxicity included skin erythema (80% of patients experienced Grade I or Grade II erythema), breast edema (72% of patients experienced mild edema), pruritus (20% of patients), and fatigue (20% of patients reported mild fatigue). One patient required a treatment break. The only late toxicity was related to long-term cosmesis. The mean overall cosmesis score for 53 patients was 9.37 (range, 8-10). Actuarial 3- and 5-year local control rates are 98%. Actuarial overall survival at 3 and 5 years are 98% and 94%. CONCLUSION: Our data indicate that treating selected women with prone breast radiotherapy is feasible and tolerated. The approach results in excellent cosmesis, and short-term outcome is comparable to traditional treatment techniques. This technique offers an innovative alternative to women who might not otherwise be considered candidates for breast conservation.

Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast cancer. Whether women with breast cancer who have inherited mutations in these genes have a different outcome after breast conservation therapy than women with "sporadic" cancer is unresolved. Consequently, we compared the outcomes after breast conservation therapy in Ashkenazi women with or without germline mutations in BRCA1 and/or BRCA2 (hereafter called BRCA). METHODS: We studied 305 women of Ashkenazi Jewish descent undergoing breast-conserving treatment for 329 invasive breast cancers. We reviewed their clinical records, retrieved their archival tissue samples, and tested those samples for the founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. Genetic results were linked to clinical data and outcomes by univariate and multivariate analyses. All Pvalues are two-sided. RESULTS: We detected mutations in BRCA genes in 28 of 305 women. Women with BRCA mutations were more likely to be diagnosed with cancer before the age of 50 years (P<.001) and to have lymph node involvement (P =.04). Ipsilateral breast tumor recurrence was more common in women with BRCA mutations, although this did not reach statistical significance (relative risk [RR] = 1.79; 95% confidence interval [CI] = 0.64-5.03). Women with mutations were more likely to develop contralateral breast cancer (RR = 3.50; 95% CI = 1.78-8.74; P =.001). Distant disease-free survival was shorter in women with mutations (66.2% versus 84.3% at 10 years; P =.05), as was breast cancer-specific survival (71.9% versus 87.2% at 10 years; P =.02). Tumor stage and nodal status, but not mutation status, were predictive of distant disease-free and breast cancer-specific survival in multivariate analysis. CONCLUSIONS: Women with BRCA founder mutations are at increased risk for breast cancer-related events after breast conservation. However, mutation status is not an independent predictor of survival and should not influence decisions regarding adjuvant therapy. The increased contralateral breast cancer risk in women heterozygous for BRCA mutations mandates careful surveillance.

Current status of tamoxifen use: An update for the surgical oncologist.

The surgical oncologist is frequently responsible for the screening and diagnosis of women with breast cancer. In this pivotal role, they are often the first to discuss treatment options, including nonsurgical interventions, with breast cancer patients. Recent long-term clinical trial data provide support for the use of tamoxifen to prevent breast cancer in women at high risk of the disease. A breast cancer risk assessment can help identify women at higher than average risk for the disease, who may be appropriate candidates for chemoprevention. It is important for the surgical oncologist to understand the current indications and evidence regarding the use of tamoxifen for breast cancer prevention and treatment as they counsel their patients on available options.

Women 35 years of age or younger have higher locoregional relapse rates after undergoing breast conservation therapy.

BACKGROUND: The use of breast conservation therapy (BCT) in young women with invasive breast cancer is controversial. To examine this important issue, rates of locoregional recurrence and overall survival after BCT were compared in two subsets of women--those < or = 35 years of age at time of surgery and their older counterparts. STUDY DESIGN: We examined records of 290 women with invasive breast cancer treated with BCT (local excision and axillary dissection) at Memorial Sloan-Kettering Cancer Center between 1984 and 1993. These included 87 patients < or = 35 years of age at time of surgery and 203 randomly selected patients > 35 years of age. Followup was obtained from physician charts or patient interviews, or both. Complete data on clinicopathologic factors, recurrence, and survival were available on 280 patients. RESULTS: Median followup from time of operation was 8.0 years for the entire group. Mean tumor size was 2.0 cm for women < or = 35 years and 1.8 cm for those > 35 (p = 0.07). Involved nodes were found in 48% of the young patients and 36% of the older patients (p = 0.08). Within our study group (n = 280), 274 patients received radiotherapy. Women < or = 35 years of age had significantly higher rates of locoregional recurrence and lower rates of overall survival than their older counterparts (p < 0.05). On multivariate analysis, these results were independent of tumor size and nodal status. A history of locoregional relapse, however, was not associated with a higher rate of death from disease in the entire cohort or in either age group. CONCLUSIONS: Patients < or = 35 years of age undergoing BCT for invasive breast cancer are at higher risk for locoregional recurrence and death from disease. The higher mortality rate, however, does not appear to be a direct result of locoregional relapse. Additional study is required to verify these findings. Currently, young age does not exclude patients from BCT in our practice. But, we include this data as part of the informed consent process.

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.

Polarization filter for biomedical tissue optical imaging.

A technique based on the degree that light is depolarized when propagating inside tissues is demonstrated for optical imaging in biomedical systems. The difference in the degree of polarization of the emerging light allows for the discrimination of different types of tissues. The technique was investigated in the transillumination and back-scattering geometry and in both cases the potential of this method to image and separate out different types of tissues is demonstrated.

The Special Surveillance Breast Program: a model of intervention for women at high risk for breast cancer.

The Special Surveillance Breast Program (SSBP) is a long-term, comprehensive, multidisciplinary program for women determined to be at high risk for the development of breast cancer. Because the women who attend this program are otherwise healthy but concerned about their risk for breast cancer, current and relevant information is required to address their concerns regarding the possibility of developing breast cancer. The purpose of this article is to describe the risk factors that indicate eligibility for the program, the structure of the program, and the results of an assessment that identified the needs of this special population.

Calcium glucarate as a chemopreventive agent in breast cancer.

Although it appears that progress is being made in the treatment of breast cancers of all stages, the etiological agents still remain unclear and render the search for preventive agents extremely difficult. What is clearly required in this situation is a nontoxic compound that can potentially affect various pathways that may be responsible for the rising incidence of breast cancer. In this review, we present the rationale for the use of an agent such as calcium glucarate, which may both change the internal hormonal milieu and also directly detoxify any environmental agents responsible for breast cancer. It is hoped that present and future clinical trials will help to better elucidate the role for this agent in the chemoprevention of breast cancer.