Breast Cancer

Several key areas must be considered in the diagnosis and managementof spinal cord compression. Because the outcome can be devastating,a diagnosis must be made early and treatment initiated promptly.Although any malignancy can metastasize to the spine, clinicians shouldbe aware that this occurs more commonly in certain diseases, ie, lungcancer, breast cancer, prostate cancer, and myeloma. The current algorithmfor early diagnosis of spinal cord compression involves neurologicassessment and magnetic resonance imaging of the entire spine.Treatment generally consists of intravenous dexamethasone followedby oral dosing. Depending on the extent of the metastases, symptomsmay also be managed with nonnarcotic pain medicines, anti-inflammatorymedications, and/or bisphosphonates, with local radiation administeredas needed. Surgery has often led to destabilization of the spine.

This study was designed to evaluate the cardiac safety of the combined treatment of HER2-positive metastaticbreast cancer patients with trastuzumab (Herceptin) plus epirubicin and cyclophosphamide (EC) incomparison with EC alone in HER2-negative metastatic breast cancer patients. Patients included those withmetastatic breast cancer without any prior anti-HER2 treatment, anthracycline therapy, or any other chemotherapyfor metastatic disease. This was a nonrandomized, prospective, dose-escalating, multicenter, openlabel,phase II study in Germany. A control group of 23 patients received EC 90/600 mg/m2 3-weekly for sixcycles (EC90 alone). A total of 26 HER2-positive patients were treated with trastuzumab, or H (2 mg/kg weeklyafter an initial loading dose of 4 mg/kg), and EC 60/600 mg/m2 3-weekly for six cycles (EC60+H); another 25HER2-positive patients received H and EC 90/600 mg/m2 3-weekly for six cycles. Asymptomatic reductions inleft ventricular ejection fraction (LVEF) of more than 10% points were detected in 12 patients (48%) treatedwith EC60 + H and in 14 patients (56%) treated with EC90 + H vs 6 patients (26%) in the EC90 alone cohort.LVEF decreases to < 50% occurred in one patient in the EC60+H cohort and in two patients in the EC90+Hcohort during the H monotherapy. No cardiac event occurred in the cohort with EC90 alone. The overallresponse rates for EC60+H and EC90+H were >60%, vs 26% for EC90 alone. The interim results of this studysuggest the cardiac safety of the combination of H with EC may be greater than that of H with AC (doxorubicin[Adriamycin]/cyclophosphamide); however, studies in larger numbers of patients are warranted. The combinationregimen revealed promising efficacy.

Adjuvant chemotherapy has been shown to be beneficial in patientswith breast cancer, and anthracycline-containing regimens are more effectivethan non–anthracycline-containing ones. The French AdjuvantStudy Group (FASG) compared FEC100 and FEC50 (fluorouracil[5-FU]/epirubicin [Ellence]/cyclophosphamide [Cytoxan, Neosar])in patients with node-positive breast cancer, with an end point of overallsurvival. After a median follow-up of 10 years, the benefit/risk ratio of theFEC100 regimen in patients with positive axillary nodes is strongly positive.Furthermore, a medicoeconomic study showed that the cost per yearof life saved was very low-approximately 1,000 euros.

The 6th University of Texas M. D. Anderson Cancer Center Investigators’Workshop was held on July 16–20, 2003, in Amelia Island, Florida.The purpose of these annual workshops has been to review the latest data onnew agents, with a particular emphasis on the broadly used agent irinotecan(Camptosar), and also novel regimens or agents.

Primary systemic therapy (ie, preoperative or neoadjuvant) increasesthe possibility for breast-conserving surgery in patients with primarybreast cancer. Patients with pathologic complete response to primarysystemic therapy have improved survival compared with those with persistenttumors. Several phase II trials have evaluated gemcitabine-containingdoublet or triplet regimens as primary systemic therapy for breastcancer, results of which have shown promising clinical and pathologicresponse rates with manageable toxicity. Results of a phase I/II studyof gemcitabine (Gemzar)/epirubicin (Ellence)/docetaxel (Taxotere), orGEDoc, with prophylactic filgrastim (Neupogen), as primary systemictherapy in 77 evaluable patients with primary breast cancer are reportedherein. Dose-limiting toxicities were grade 3 febrile neutropenia(n = 1) and grade 3 diarrhea (n = 2) at the fourth dose level ofGEDoc tested (gemcitabine at 800 mg/m2 days 1 and 8, epirubicin at90 mg/ m2 day 1, and docetaxel at 75 mg/m2 day 1). As assessed byultrasound, 92% of patients responded overall (22% complete response),and 79% of patients could undergo breast-conserving surgery. Thepathologic complete response rate in resected breast tissue was 26%.

Use of the gemcitabine (Gemzar) plus docetaxel (Taxotere) combinationin metastatic breast cancer is motivated by the different mechanismsof action of the drugs, partially nonoverlapping toxicity profiles,and good single-agent activities of both drugs in treatment-naive andanthracycline-pretreated patients. In phase II trials, combinations ofgemcitabine at 900 or 1,000 mg/m2 on days 1 and 8 and docetaxel at 75to 100 mg/m2 on either day 1 or day 8 every 3 weeks, or gemcitabine at800 mg/m2 on days 1, 8, and 15 and docetaxel at 35 mg/m2 on days 1, 8,and 15 or 100 mg/m2 on day 1 every 4 weeks, have produced responserates of 36% to 79% in patients receiving primarily second-line treatment;response rates were greater than 50% in five of six studies. Inphase II trials using every-2-week regimens of gemcitabine at 1,500 or2,000 mg/m2 on day 1 and docetaxel at 50 or 65 mg/m2 on day 1 or 55mg/m2 on day 8, response rates were 50% in pretreated patients and66% in treatment-naive patients. Neutropenia is the primary toxicity ofthe combination; in phase II studies performed with or without growthfactor support, rates of grade 3/4 neutropenia ranged from 29% to 79%and rates of febrile neutropenia ranged from 0% to 18%. An ongoingphase III trial is comparing gemcitabine at 1,000 mg/m2 on days 1 and8 plus docetaxel at 75 mg/m2 on day 1 every 21 days, vs capecitabine at1,000 mg/m2 twice daily for 14 days plus docetaxel at 75 mg/m2 on day1 every 21 days in patients with metastatic breast cancer. Results of thistrial will help to determine optimal use of taxane-based combinationsin patients with advanced disease.

Although anthracyclines and the taxanes comprise the most activefirst-line cytotoxic treatments in patients with hormone-insensitive orlife-threatening metastatic breast cancer, many patients progress andrequire other chemotherapeutic agents. Development of new combinationsand/or agents is thus needed. Gemcitabine (Gemzar) and platinumcompounds have been employed as single agents, and the additionof gemcitabine to the platinums results in significant clinical benefitand response rates. Correlative biologic studies are expected fromseveral already-reported trials and may help elucidate predictive factorsfor both response and toxicity when combining gemcitabine andthe platinums. Trials incorporating these doublets in earlier stages ofbreast cancer or in the neoadjuvant setting may further elucidate theirrole in breast cancer treatment.

The rapid emergence of gemcitabine (Gemzar) as a viable component inchemotherapy for breast cancer is indeed an encouraging development.Specifically, until relatively recently, the focus of research and treatmentwith gemcitabine was primarily on lung cancer. Growing opinion amongmany experts in breast cancer held that studies of gemcitabine in breast cancer werenoticeably lacking and that such research was warranted. Fortunately, these voiceswere heard, and the manufacturers of gemcitabine responded with an acceleratedinitiative to explore further the role of gemcitabine in breast cancer. Rapid progresswas made.

Gemcitabine (Gemzar) possesses meaningful antitumor activity inthe treatment of breast cancer, repeatedly demonstrating superior outcomeswithout the price of excessive toxicity in most patients. In combinationwith other agents, it has a potential for nonoverlapping toxicities,a novel mechanism of action, as well as a potential lack of completecross-resistance. Randomized phase III trials with gemcitabinehave yielded response rates that have translated into time to diseaseprogression and survival benefits. Thus, enthusiasm continues forgemcitabine, especially in combination with other cytotoxic agents. Theaugmentation of efficacy (ie, response rates, time to disease progression,overall survival) by the addition of gemcitabine to paclitaxel hasestablished this regimen as a first-line treatment option for patientswho might benefit from combination therapy. Gemcitabine now remainsunder active investigation for the treatment of early-stage breastcancer, with ongoing trials characterizing its role in the neoadjuvantsetting.

The tAnGo trial is a randomized, open-label, multicenter phase IIItrial examining adjuvant treatment with epirubicin (Ellence)/cyclophosphamide(Cytoxan, Neosar) for four cycles followed by paclitaxel aloneor combined with gemcitabine (Gemzar) for four cycles in patients withearly-stage breast cancer. In the Cancer and Leukemia Group B(CALGB) 9344 trial, addition of paclitaxel to anthracycline/cyclophosphamideadjuvant therapy resulted in increased time to recurrence andimproved survival. Because an unplanned subgroup analysis in CALGB9344 indicated a significant benefit of paclitaxel in patients with estrogenreceptor (ER)-negative disease but not ER-positive disease, the initialtAnGo trial design called for enrollment of patients with ER-negativedisease. The tAnGo trial entry criteria were recently amended toallow any ER status, given experience suggesting that clinical benefitof taxane-containing regimens in ER-positive disease may emerge overa time frame longer than that required to detect benefit in ER-negativedisease. Gemcitabine has been included as a partner for paclitaxel inthe tAnGo trial based on high response rates, including high completeresponse rates, observed in phase II trials of the combination in moreadvanced disease and based on the tolerability and safety of the combinationcompared with those of other taxane-containing two-drug combinations.The tAnGo trial is currently accruing patients and has atarget population of 3,000. Trial results should provide important informationon the role of gemcitabine in adjuvant therapy for breastcancer.

Trastuzumab (Herceptin) is an effective treatment in patients withHER2-overexpressing metastatic breast cancer. Risk of trastuzumabinducedcardiotoxicity raises concerns regarding combined use withanthracyclines or other potentially cardiotoxic agents followinganthracycline treatment. We characterized interactions betweentrastuzumab and gemcitabine (Gemzar) and the combination ofgemcitabine and cisplatin or carboplatin (Paraplatin) as such combinationsmight help reduce the risk of cardiotoxicity. Multiple drugeffect/combination index isobologram analysis was used to study theefficacy of chemotherapeutic drug plus trastuzumab combinations inHER2-overexpressing breast cancer cell lines. Combination index valueswere derived from parameters of the median effect plots, and statisticaltests were used to determine whether the mean combinationindex at multiple effect levels significantly differed from a combinationindex value of 1.0 (values < 1.0 indicate synergy; values > 1.0,antagonism; values equal to 1.0, additivity). At a wide range of clinicallyachievable drug concentrations, interactions between trastuzumaband gemcitabine were synergistic at low concentrations of gemcitabineand antagonistic at high concentrations. A consistent synergistic interactionwas observed with the three-drug combination of trastuzumabplus gemcitabine plus carboplatin or cisplatin. Available clinical dataon the use of trastuzumab plus gemcitabine, and trastuzumab plusgemcitabine/paclitaxel, as well as clinical data on the use ofgemcitabine/cisplatin in breast cancer, are discussed. These findingsindicate that trastuzumab plus gemcitabine and trastuzumab plusgemcitabine plus cisplatin or carboplatin are rational combinations toevaluate in clinical trials.

Gemcitabine (Gemzar) and paclitaxel are active drugs in the treatmentof metastatic breast cancer. Phase I clinical trials data have suggestedthat the gemcitabine plus paclitaxel combination is safe in breastcancer patients. Two doses/administration schedules have been preferredin subsequent phase II and III trials: gemcitabine on days 1 and8 plus a taxane on day 1, every 3 weeks; or gemcitabine plus a taxaneon days 1 and 14, every 4 weeks. In phase II trials, 114 of 221 patients(52%) responded to gemcitabine/paclitaxel therapy. Response rates werelower among patients who received previous chemotherapy for metastaticdisease (response rates: 45%, second line and 70%, first line).Toxicity of gemcitabine/paclitaxel regimens has generally been low, withfew cases of neutropenia or nonhematologic toxicity. Results of therandomized phase III registration trial show a clear advantage forgemcitabine plus paclitaxel over paclitaxel alone in time to disease progression,objective response, and overall survival. Triplet combinations,in which an anthracycline is added to gemcitabine/paclitaxel, are beingexplored in the metastatic and neoadjuvant settings.

MILAN, Italy-In women with fibroglandular or dense breasts, magnetic resonance imaging (MRI) is more sensitive than mammography for detection of multiple malignant foci, suggesting that a dynamic MRI examination is warranted before treatment planning in this group of patients, a team of Italian radiologists and surgeons has concluded. Yet in breasts with an almost completely fatty pattern, both techniques had comparable sensitivity, their multicenter, prospective, nonrandomized study showed. Further, while MRI achieved a 17% gain in sensitivity over mammography in detection of invasive foci, the two techniques had similar sensitivity in detection of in situ foci, and neither had a strong positive predictive value (PPV), the researchers found.

ROCKVILLE, Maryland-The FDA has approved a new indication for Eloxatin (oxaliplatin for injection, Sanofi-Synthelabo)-as a treatment combined with conventional chemotherapy for the postsurgical treatment of patients with stage III colon cancer after complete tumor resection. The drug, as with its previous two US approvals, is to be used in combination with infusional fluorouracil/leucovorin (5-FU/LV). The company noted that the supplemental approval provides the first new adjuvant treatment for colon cancer in more than a decade.

ROCKVILLE, Maryland-Femara (letrozole tablets, Novartis) has received marketing approval from the US Food and Drug Administration (FDA) for the extended adjuvant treatment of postmenopausal women with early breast cancer who have received 5 years of adjuvant therapy with tamoxifen. The FDA based its approval on data from the MA-17 trial, an international, independent study supported by Novartis.

This year alone, more than 215,000 women in the United States will bediagnosed with, and over 40,000 will die from, invasive breast cancer.Recently, mortality from female breast cancer has declined despite anincrease in its incidence. This decline corresponds with improved screeningfor prompt tumor detection, and advances in the treatment of earlydisease. Of these, endocrine therapy has played a prominent role. Forwomen with estrogen receptor (ER)-positive and/or progesterone receptor(PR)-positive breast cancers, endocrine therapy has proven to be amajor component of adjuvant therapy, but it is not effective in womenwhose breast cancers lack ERs and PRs. The selective estrogen-receptormodulator (SERM) tamoxifen has been well established as safe and effectivein the adjuvant care of both pre- and postmenopausal women withhormone-receptor–positive early breast cancer. For premenopausalwomen, ovarian suppression is an important option to be considered.Additionally, the aromatase inhibitors have recently demonstrated utilityin postmenopausal women. The ideal sequencing of treatment withtamoxifen and/or an aromatase inhibitor is the subject of several ongoingstudies. Factors involved in selecting an appropriate endocrine regimenhave grown considerably over the past decade. It is becoming more importantfor those caring for women with breast cancer to fully understandthe available endocrine treatment options and the prognostic and predictivefactors available to help select the most appropriate treatment. Thegoal of this article is to assist clinicians in making decisions regardingadjuvant hormonal therapy and to provide information regarding availableclinical trials. To achieve this, the therapeutic options for hormonaltherapy will be reviewed, as will prognostic and predictive factors used inmaking decisions. Finally, four cases illustrating these difficult decisionswill be discussed, with recommendations for treatment.

Dr. Eneman and colleagues providea thorough and timely reviewof adjuvant endocrinetherapy for hormone-receptor–positiveearly breast cancer. This field is rapidlyshifting, with the accumulation of recentlypresented and published datafrom randomized trials in both pre- andpostmenopausal patients. As with mostnew clinical research data, findingsfrom these recent trials raise as manyquestions as they provide conclusions.A few of the issues discussed in thiswell-written review deserve comment.

Our understanding of the biologyof breast cancer has undoubtedlyimproved in the pastdecade, and remarkable progress hasbeen achieved in its treatment. Thosecaring for these patients have longrealized that breast cancer is a diseasewith an extremely diverse natural history,and much remains to be learnedabout the interaction among knownpredictive and prognostic factors. Notlong ago, the “more is better” strategyexemplified by high-dose chemotherapy(often resulting in high-dose toxicity)dominated the research agendaand clinical practices of many institutions.Although a minimum chemotherapydose intensity is required[1]and increasing the frequency of specificregimens is advantageous,[2] furtherdose intensification with[3] orwithout stem cell rescue[4-6] offersno meaningful benefit in the adjuvantsetting.

Pemetrexed (Alimta) is a novel folate antimetabolite that primarilyinhibits the enzymes thymidylate synthase (TS), dihydrofolate reductase(DHFR), and glycinamide ribonucleotide formyl transferase(GARFT), all of which are involved in pyrimidine and purine synthesis.In a phase II trial of patients with T3/4, N0–2 breast cancer, expressionof thymidylate synthase (TS), dihydrofolate reductase (DHFR),glycinamide ribonucleotide formyltransferase (GARFT), p53, andc-erb-B2 (at the mRNA or protein level) was examined in tumor biopsyspecimens before and 24 hours after the first dose of pemetrexed andafter three cycles of single-agent treatment to establish correlations ofbiomarker levels and changes with clinical outcome and toxicity. Althoughfinal data are not available, initial indications are that clinicalresponse may correlate with decreased or low TS expression. The resultsobtained from clinical data are supported by laboratory results inthree cell lines (MDA-231, MCF-7, and ZR-75). These results suggestthat in vitro transcript profiling to identify which genes are importantpredictors of successful cytotoxic chemotherapy, followed by a focusedclinical trial to confirm the in vitro results, may be the best approachfor translational research.

Pemetrexed (Alimta) is a novel antimetabolite that inhibits the folatedependentenzymes thymidylate synthase, dihydrofolate reductase, andglycinamide ribonucleotide formyltransferase. Pemetrexed has demonstratedactivity in clinical trials in a variety of tumor types, includinglung, breast, colon, mesothelioma, pancreatic, gastric, bladder, headand neck, and cervix. Pemetrexed is rapidly metabolized into activepolyglutamate forms that are potent inhibitors of several tetrahydrofolatecofactor-requiring enzymes critical to the synthesis of purines and thymidine.Functionally, pemetrexed acts as a prodrug for its polyglutamateforms. Two different transporters are known to take extracellular folates,and some antifolates, into the cell. These are the reduced folate carrierand the folate receptor. One of the many attributes that make pemetrexedunique is that methodology has been developed to eliminate and controlmany of its associated clinical toxicities. Multivariate analyses demonstratedthat pretreatment total plasma homocysteine levels significantlypredicted severe thrombocytopenia and neutropenia, with orwithout associated grade 3/4 diarrhea, mucositis, or infection. Routinevitamin B12 and folic acid supplementation have resulted in decreasedfrequency/severity of toxicities associated with pemetrexed without affectingefficacy, making this novel antifolate a safe and efficaciousanticancer agent.

Pemetrexed (Alimta) is an antifolate that is effective in the inhibitionof multiple enzyme targets including thymidylate synthase,dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase.The compound has been evaluated in several phase I trials, bothas single agent and in combination with other cytotoxic agents. Theinitial schedule selected for further investigation in phase II trials waspemetrexed 600 mg/m2 as a 10-minute infusion on day 1 every 21 days.During the subsequent phase II development, the dose of pemetrexedwas adjusted to 500 mg/m2 due to bone marrow and gastrointestinaltoxicities. The adjusted dose of pemetrexed was well tolerated throughoutthe late-phase drug development program. Preclinical evidencesuggests that pemetrexed has additive or synergistic activity when combinedwith many other clinically important anticancer agents, includinggemcitabine (Gemzar), fluorouracil, carboplatin (Paraplatin),oxaliplatin (Eloxatin), paclitaxel, and vinorelbine (Navelbine). Doselimitingtoxicities in these studies were primarily hematologic, and therewas no evidence of cumulative hematologic toxicity. During the drugdevelopment program it was discovered that supplementation with folicacid and vitamin B12 profoundly increased the tolerability ofpemetrexed. The studies discussed in this review demonstrate thatpemetrexed is well tolerated as a single agent and will be an importantcontribution to combination chemotherapy regimens.

Pemetrexed (Alimta) is active in a variety of solid tumors, includingbreast and gynecologic cancers. Phase II trials of pemetrexed at a doseof 600 mg/m2 without vitamin B12 and folic acid supplementation inlargely pretreated metastatic breast cancer patients demonstrated objectiveresponse rates of 21% and 28%, with generally manageableneutropenia constituting the primary toxicity. In phase II trials using500 mg/m2 with or without vitamin supplementation in anthracyclineandtaxane-pretreated patients, response rates were lower (approximately9%) and treatment was generally well tolerated irrespective ofvitamin supplementation status. A phase II trial is currently comparingpemetrexed doses of 600 and 900 mg/m2 with vitamin B12 supplementationin patients with previously untreated advanced breast cancer. In aphase II trial in patients with advanced cervical cancer, pemetrexed at600 mg/m2 without vitamin supplementation and 500 mg/m2 with supplementationproduced similar response rates, with the frequency of neutropeniabeing somewhat lower among patients receiving the lower doseand vitamin supplementation. Preliminary results in an ongoing phaseII trial indicate activity of the regimen of gemcitabine (Gemzar) at1,000 mg/m2 plus pemetrexed at 500 mg/m2 with vitamin supplementationin patients with ovarian cancer. Ongoing and future studies willestablish optimal dosing regimens of pemetrexed and potential benefitsof vitamin supplementation in the settings of metastatic breastcancer and gynecologic malignancies.

NEW ORLEANS-Testing for a specific gene polymorphism may help to identify which patients are candidates for treatment with aromatase inhibitors, according to a presentation at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 507).

Six published randomized trials[1-6] and one meta-analysis[7] of published and unpublishedtrials have demonstrated thatbreast-conserving therapy (breast-conservingsurgery plus breast irradiation)is equivalent to mastectomy interms of survival. As a result, breastconservingtherapy is the option preferredby many women for thetreatment of early-stage breast cancer.[8] Breast irradiation followingbreast-conserving surgery is an integralpart of breast-conserving therapy.There are seven other publishedrandomized trials demonstrating thatbreast irradiation substantially reducesthe rate of local recurrence andprevents the need for subsequent mastectomy.[9-15] A recent meta-analysisalso supports the conclusion that breastcancer patients who receive breast irradiationhave improved survival.[16]

Dr. Arthur and colleagues havepresented a comprehensiveoverview of two of the mostnoteworthy radiotherapy (RT) advancesin the contemporary managementof breast cancer, ie, short-course hypofractionatedRT and intensity-modulatedradiotherapy (IMRT). Althoughboth challenge the conventional RTapproach to early-stage disease, theydiffer considerably in that hypofractionatedRT refers to treatment of eitherthe entire breast or a part of thebreast in a shorter time course thanwith standard fractionation, whereasIMRT refers to an alteration in themethod of treatment delivery. I willdiscuss each in turn.

Conventional radiotherapeutic treatment for early and advancedbreast cancer has been based on broad-field radiation treatment principlesthat date back several decades. Although these strategies havebeen successful, newer techniques now offer the ability to incorporateimproved target imaging, dosimetric planning, and treatment deliveryinto the treatment design. These newer techniques include acceleratedpartial-breast irradiation and hypofractionated whole-breast irradiationfor early-stage breast cancer, and intensity-modulated radiotherapy(IMRT) for both early and advanced breast cancer. Accelerated partial-breast irradiation and hypofractionated whole-breast radiotherapyare treatment approaches that promise both reduced overall treatmenttimes and the potential for increased use of breast-conservation therapy.IMRT offers unparalleled dose homogeneity and conformality thatenables dose reduction to normal structures with the potential to reducetreatment toxicity and improve cosmesis. Based on the publishedliterature, an increasing number of treatment facilities are offering treatmentwith these techniques. However, further clinical study remainsimportant to thoroughly define the appropriate clinical setting, patientselection criteria, and limitations for each of these innovative treatmentapproaches.

NEW ORLEANS-Addition of trastuzumab (Herceptin) to standard anthracycline-containing chemotherapy in the neoadjuvant setting led to a dramatic increase in the frequency of pathological complete remissions in patients with operable HER-2-positive breast cancer. Aman Buzdar, MD, professor of breast medical oncology, M.D. Anderson Cancer Center, presented the results of the phase III trial at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 520).

NEW ORLEANS-By monitoring the levels of circulating tumor cells (CTCs) in peripheral blood, it is possible to predict which patients with metastatic breast cancer will progress rapidly while on apparently futile therapy, Daniel F. Hayes, MD, of the University of Michigan Comprehensive Cancer Center, Ann Arbor, said at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 509).

This excellent and practical articleby Dr. Ravdin is worthwhilereading for every physician involvedin the long-term care of womenwith a previous diagnosis of breastcancer. Dr. Ravdin clearly outlinesthe theoretical rationale underlying theincreased risk of osteopenia and osteoporosisin women with a history ofbreast cancer. The fact that such womencommonly undergo prematuremenopause either deliberately, as partof treatment for breast cancer, or as asecondary effect of chemotherapy, andthat estrogen-replacement therapywith or without progesterone remainscontraindicated for fear of increasingthe risk of recurrence, clearly contributesto the increased possibility ofdeveloping osteopenia or osteoporosis.New data supporting the role ofaromatase inhibitors in adjuvant therapy[

The authors present a comprehensivereview of anthracycline-based adjuvant chemotherapyregimens, supporting the useof these regimens over CMF (cyclophosphamide[Cytoxan, Neosar],methotrexate, fluorouracil [5-FU]) inearly-stage breast cancer. They concludethat the addition of taxanes toanthracycline-containing regimens innode-positive disease may conferadditional benefit. Newer regimenscontaining taxanes and other agentsthat omit the use of anthracyclinesshow promise but are still underinvestigation.