My Take on…
Expert clinical commentary on noteworthy new studies
Thursday, August 27, 2015
DCIS: Time to Change Our Standard of Care?
BY CYNTHIA X. MA, MD, PHD
Associate Professor of Medicine
Clinical Director of the Breast Program
Section of Medical Oncology
Washington University, Saint Louis
Ductal carcinoma in situ (DCIS) of the breast refers to a heterogeneous group of “cancerous” or neoplastic lesions that reside within the mammary ducts and lobules. DCIS is frequently an incidental finding as abnormal-appearing microcalcifications on screening mammogram and represents about 20 percent of breast cancer diagnoses each year, and is therefore a significant public health issue.
DCIS is an important diagnosis as it is generally accepted that it is a direct precursor of invasive breast cancer (IBC) based on a multitude of evidence. For example, nearly all IBCs are found adjacent to DCIS on histologic examination. In the small number of studies using paired DCIS and IBC from the same breast, similar genomic alterations were observed, although there was an overall trend toward an increase in the number of genetic alterations in IBC.
The risk factors for DCIS are similar to those of IBC. The natural history of DCIS to evolve to IBC has also been demonstrated in long-term follow-up studies of patients with retrospectively recognized DCIS that was incompletely excised. In these studies, IBC was subsequently diagnosed at the same site as the index lesion in up to 50 percent of the cases with prolonged follow-up.
With the above information, DCIS has been generally accepted as a surgical disease, and current guidelines for the treatment of DCIS recommend complete surgical excision with negative margins. The advent of radiation followed by lumpectomy reduced the risk of recurrence of both invasive and non-invasive recurrence, and led to less disfiguring surgery such as mastectomy. This approach effectively reduced ipsilateral invasive and non-invasive recurrence. For ER+ disease, tamoxifen or aromatase inhibitors have also been shown to further reduce recurrence, although there is no impact on survival.
However, the recent JAMA Oncology publication by Narod et al has raised concerns with this seemingly logical approach. In this large observational study which included 108,196 women diagnosed with DCIS between 1988 and 2011 in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, an extremely low breast cancer specific mortality of 3.3 percent (95% CI, 3.0%-3.6%) overall was observed. Radiation therapy following lumpectomy reduced the risk of ipsilateral IBC recurrence, but did not impact breast cancer specific survival.
Interestingly, half of the recurrences were in the contralateral breast and 517 patients died of breast cancer without an in-breast invasive recurrence. In addition, although high-grade DCIS was associated with increased breast cancer mortality, it was not associated with an increased risk of ipsilateral invasive recurrence compared with low-grade DCIS.
Young age (<35 years) (7.8% vs. 3.2%; HR, 2.58 [95%CI, 1.85-3.60]; P < 0.001) and black ethnicity (7.0% vs. 3.0%; HR, 2.55 [95%CI, 2.17-3.01]; P < 0.001) were associated with significantly higher risk of breast cancer specific mortality compared with that in older women and non-Hispanic whites, respectively. Other important risk factors included ER status, high grade, tumor size, and comedonecrosis.
In addition, similar to the recurrence pattern observed in IBC, ER-negative DCIS associated recurrence is often within the first 10 years after diagnosis, while ER+ DCIS was associated with a slower but persistent risk of recurrence during the follow-up.
Results Raise Important Issues that Challenge Current Paradigm
Despite potential limitations associated with observational studies using the SEER data bases, including the lack of formal pathology review, information regarding resection margin and adjuvant hormonal therapy, and the possibility of underestimating the non-invasive breast cancer recurrence due to coding issues, results from the study raised important issues that challenge the current screening and treatment paradigm of DCIS.
It is clear that:
(1) some DCIS may never progress to IBC in a women’s life time;
(2) some DCIS may progress slowly over years to come; and
(3) some DCIS, however, could take an aggressive course, with simultaneous occurrence or early metastatic dissemination of invasive disease with or without in-breast diagnosis of IBC.
For patients with DCIS in the first two categories, perhaps watchful waiting or approaches to delay the progression is an acceptable option, while for those with DCIS in the third categories, local therapy is necessary, but more effective systemic therapy that prevents or eliminates metastatic spread of potential invasive disease is crucial to prevent subsequent breast cancer morbidity and mortality.
The question is how do we risk-stratify patients into these categories. Clinical and pathologic parameters, including age, ethnicity, ER and HER2 status, grade, tumor size, and presence or absence of comedonecrosis, perhaps could guide in our decisions in future practice.
We encourage participation in clinical trials. The CALGB 40903 (schema below) will determine which subsets of ER+ DCIS might be most amenable to systemic treatment so that surgery could be avoided. It is a single-arm trial for postmenopausal women with ER+ DCIS, who will be treated with letrozole and monitored for six months followed by surgery for biomarker changes.
For high-risk HER2+ DCIS, NSABP B-43, a phase III study that compares trastuzumab given concurrently with radiation therapy with radiation alone for women with HER2+ DCIS resected by lumpectomy, has completed enrollment. Perhaps strategies like trastuzumab or other targeted agents are the key to eliminate the potential for IBC and metastatic spread.
In conclusion, the diagnosis of DCIS has significant implications on an individual patient’s risk of subsequent invasive breast cancer, either derived from this DCIS or not, but in general DCIS carries a low breast cancer specific mortality risk. However, a small number of patients have high-risk disease that mandates aggressive treatments.
We must recognize the highly heterogeneous biology and behavior of DCIS. Accumulating evidence from population studies and clinical trials calls for reconsideration of the current screening and treatment paradigm. An individualized risk-assessment tool and treatment strategy, however, is needed to assist clinical decision-making.
Monday, May 12, 2014
BY RAMASWAMY GOVINDAN, MD
The recently concluded American Association for Cancer Research (AACR) Annual Meeting featured several insightful presentations relevant to novel therapeutics. Due to space constraints, I have selected only a few for discussion here.
Palbociclib, an inhibitor of cyclin dependent kinases (CDK) 4 and 6 improved progression-free survival (PFS) in patients with previously untreated ER+, HER2- metastatic breast cancer (Abstract CT101). Preclinical studies with palbociclib have shown decreases in cell proliferation and cellular DNA synthesis due to inhibition of Rb phosphorylation resulting in cell cycle arrest in G1 phase. Moreover, palbociclib preferentially inhibited proliferation of luminal estrogen receptor positive human breast cancer cell lines.
PALOMA-1 is a Phase II study that randomized 165 postmenopausal patients with metastatic breast cancer to receive palbociclib and letrozole or letrozole alone. The median progression-free survival with the combination therapy was 20.2 months versus 10.2 months with letrozole alone (HR-0.488, p=0.0004). Overall survival favored the combination therapy, although the differences were not statistically significant (37.5 months vs. 33.3 months, HR- 0.813, p=0.2105).
The most common adverse events included neutropenia, leukopenia, fatigue, and anemia. Alterations in cyclin D1 and/or p16 did not identify a subgroup of patients who had greater benefit with palbociclib.
Two large ongoing Phase III studies are evaluating the role of palbociclib in patients with breast cancer--one in advanced-stage (PALOMA-3) and another in early-stage disease (PENELOPE-B).
Results from a Phase I study of another inhibitor of CDK 4 and 6, LY2835219, were also presented at this meeting (Abstract CT232). Patients with five different tumor types (glioblastoma, melanoma, and cancers of the lung, colon/rectum, and breast) were enrolled. The activity of the agent in 47 patients with heavily pretreated metastatic breast cancer (the median number of previous treatments was seven) was impressive, with the partial response rate of 19 percent and disease-control rate of 51 percent. The disease control rate was 81 percent for patients with HR+ disease.
The median progression-free survival time was 5.8 months for all patients with breast cancer and 9.1 months for HR+ patients. If additional studies confirm these early promising results, CDK4/6 inhibitors may play a key role in breast cancer and hopefully in other malignancies as well. We should make every effort to identify biomarkers to select rationally for this class of compounds.
An investigational agent, DEDN6525A, an antibody-drug conjugate, showed some early signs of activity in patients with malignant melanoma in a Phase I study (Abstract CT233). DEDN6525A is a conjugate of antibody against the endothelin B receptor (ETBR) and chemotherapy monomethyl auristatin (MMAE). Nearly 50 percent of melanoma cells express ETBR.
In this Phase I study, 12 of the 19 patients who received 1.8 mg/kg of DEDN6526A had either a partial response or stable disease for six or more months. The most common side effects were infusion-related reactions, fatigue, neutropenia, and neuropathy.
The recommended Phase II dose for this agent is 2.4 mg/kg administered every three weeks. Data analysis from the expansion cohort is ongoing.
Results from another Phase I study reported at the meeting highlighted the potential of a new form of immunotherapy. IMCgp100 is a novel agent with an affinity-enhanced T cell receptor (TCR) specific for the HLA-A2 restricted melanoma gp100 peptide (YLEPGPVTA) fused to an anti-CD3 antibody.
IMCgp100 seems to direct T cell cytotoxicity even in the face of significant levels of PD-1 and PDL-1. Patients with advanced melanoma who are HLA A2 positive and not ideal candidates for vemurafenib were enrolled in this Phase I study (Abstract CT329). Four partial responses were observed so far, including three lasting for more than nine months in this very early analysis. Toxicities included skin rash, pyrexia, and hypotension.
These studies raise the hope that options for patients with malignant melanoma (and possibly other cancers) would continue to increase in the coming years.
Several studies have reported activity of PD-1 and PDL-1 inhibitors in patients with melanoma and lung cancer over the past few years. Efforts are ongoing to identify patients who are likely to respond to the drugs that inhibit immune checkpoint.
In a study presented at the AACR meeting, patients with advanced malignant melanoma who received MK-3475 whose tumor cells were “positive” for PDL-1 had a 49 percent response rate compared with only 13 percent in those who were “negative” for PDL-1 (Abstract CT104). These data were derived from 195 patients enrolled in the Phase I study of MK-3475 at three different doses.
Tumor samples were considered positive if at least one out of 100 cells had expression of PDL-1 protein. Of 125 evaluable tumor samples 71 percent were positive for PDL-1. The response to MK-3475 in the PDL-1 positive group was the same regardless of whether patients were treated with ipilimumab or not.
In a related presentation, response rates in patients with advanced NSCLC with MK-3475 were higher in those with PDL-1 positive tumors than in those with PDL-1 negative tumors (37% vs. 11%) (Abstract CT105). By using a stringent criterion of requiring 50 percent of the cells stained for PDL-1 to define the “high score” group, the response rate (by RECIST) was 37 percent in the “high” score group compared with only 11 percent in the low score (or negative) group. The differences in the response rates were reflected predictably in six month PFS (41% vs. 17%, HR- 0.53, 95% CI: 0.33-0.83, p=0.004).
Data from two ongoing studies will be used to validate these findings in patients with NSCLC.
Mutations involving isocitrate dehydrogenase (IDH) 2 have now been reported in acute myeloid leukemia (AML), myelodysplastic syndrome, and other malignancies. Cancer-associated IDH2 mutants produce 2-hydroxyglutarate (2-HG), which blocks normal cellular differentiation.
AG-221 is a first-in-class compound that blocks the activity of mutated IDH2 enzyme and decreases the level of 2-HG. In this Phase I trial, patients with AML and MDS with IDH2 mutation received AG-221 (Abstract CT103).
It is remarkable that six of the seven evaluable patients had objective responses, with significant decrease in the levels of 2-HG (90% decline in patients with R140Q mutation). In addition, the investigators found evidence of maturation in the bone marrow consistent with pre-clinical studies. AG-221 is well tolerated.
Although these results are preliminary, targeting IDH2-mutant leukemia may soon become possible in the clinic.
In summary, it is heartening to see that a number of novel therapies are being developed to treat patients with a wide variety of malignancies, moving findings from the laboratory to the clinic at an impressive pace. I would encourage readers to visit the AACR webcast website (webcast.aacr.org) to hear some (or most) of these inspiring and instructive presentations.
Tuesday, April 16, 2013
BY RAMASWAMY GOVINDAN, MD
Clinical Advisory Editor for Oncology, Oncology Times;
Co-Director, Section of Medical Oncology
Professor of Medicine, Division of Oncology
Washington University School of Medicine
St. Louis, Missouri
Over the past decade, prospective studies have clearly demonstrated that certain specific mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) are associated with dramatic response to EGFR TK inhibitors in patients with non-small cell lung cancer (NSCLC). Since the initial recognition six years ago, the presence of EML4-ALK translocation has now been shown to identify a subgroup of patients likely to respond to crizotinib. However, as is nearly always the case, translating these research findings to clinical practice remains a challenge.
Several questions linger despite copious amounts of research work in this area. For starters:
- Should we screen all patients with NSCLC for molecular alterations?
- What specific molecular tests should be done?
- Can KRAS mutation analysis be used to select patients for anti-EGFR therapy?
- What standards should the laboratories follow?
- What is the optimal turn around time?
These issues transcend the traditional boundaries of medical practice and involve pathologists (anatomical, molecular), pulmonologists, thoracic surgeons, interventional radiologists, and medical and radiation oncologists.
In the absence of well-defined prospective clinical trials to address each and every one of these practice issues related to molecular testing, a comprehensive review of the published literature overseen by unbiased experts cutting across a wide variety of disciplines is perhaps the best way to guide practicing physicians and the lung cancer community. Accordingly, a team of experts convened by the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association of Molecular Pathology (AMP) has recently completed such an endeavor.
The team reviewed published data before developing guidelines for EGFR and ALK molecular testing in patients with lung cancer. These findings were published jointly in Archives of Pathology and Laboratory Medicine, The Journal of Molecular Diagnostics and the Journal of Thoracic Oncology.
The expert panel screened 1,533 abstracts to identify 521 pertinent articles for detailed review. The members of the panel formulated initial recommendations at a public meeting. An advisory panel reviewed draft versions of the recommendations. Based on the strength of the data the recommendations were graded. Grades A or B were assigned when the available data are strong enough to support clinical practice in all or most situations. When the data are insufficient (Grades C or D), expert consensus option was used. All members completed the CAP conflict-of-interest process. Only members with no real or perceived conflict of interest served as authors on the expert panel. The CAP, IASLC, and AMP organizations provided the funding for this effort. No industry funding was used for this project.
The clinical practice guideline (CPG) with regard to molecular testing of EGFR and ALK in patients with lung cancer addressed five principal and 14 corollary questions. The key questions:
1. When should molecular testing for NSCLC performed?
2. How should EGFR testing be performed?
3. How should ALK testing be performed?
4. Should other genes be routinely tested in lung adenocarcinoma?
5. How should molecular testing of lung adenocarcinoma be implemented and operationalized?
The panel felt there was sufficient evidence to recommend that EGFR molecular testing and ALK testing in patients with lung adenocarcinoma. The clinical characteristics (age, gender, ethnicity, and smoking status) are not sufficiently specific to identify a subgroup of patients more likely to harbor these molecular alterations. However, in the setting where only a limited amount of material is available (small core biopsies and cytological specimens) where an adenocarcinoma component cannot be completely ruled out, EGFR and ALK testing are recommended in patients who are young and report no history of tobacco smoking.
The panel felt that the quality of specimens (tumor content and preservation) matters more than whether they are obtained from primary or metastatic lesions. The recommendation is that EGFR and ALK testing be done at the time of the diagnosis of metastatic disease. The tissue should be prioritized for EGFR and ALK testing after a diagnosis of lung adenocarcinoma is established.
In the absence of data, the consensus opinion from this expert panel determined that the optimal turn-around time was two weeks (10 working days). The panel also addressed the issues of how the specimens should be processed for EGFR mutation testing, the minimum proportion and number of cancer cells needed for mutation detection.
The panel advised against using EGFR testing using immunohistochemistry or copy number analyses (FISH or chromogenic in situ hybridization) instead of EGFR mutation testing. The panel does not recommend using KRAS mutation testing alone as a sole determinant of anti-EGFR therapy given the lack of significant benefit in EGFR wild subgroup (regardless of KRAS mutation status) with upfront EGFR TK inhibitors.
The panel recommends use of an ALK FISH assay using dual-labeled break-apart probes. The consensus opinion favors the involvement of a pathologist to choose the most appropriate slides for the ALK FISH test. The expert panel felt that the published data are insufficient at the present time to develop guidelines for testing other molecular markers in lung cancer. In addition, the panel addressed other issues related to testing, validation, reporting, and quality assurance.
Reflex testing, an approach that does not require a specific order from the clinician, was deemed appropriate by the panel if agreed upon by the (institutional) lung cancer care team in order to expedite the test results. However, it is worth remembering that sometimes the initial core biopsies with limited material may be followed by a more complete resection. A reflex testing done on a smaller core needle biopsy with a poor-quality specimen may not yield optimal results compared with the test done on a larger resected specimen.
A robust communication system should be put in place in order to optimize the process between the clinicians and pathologists. I commend the panel for taking this opportunity to remind the pathology community that the term “non-small cell lung carcinoma” is no longer an acceptable pathological diagnosis for resected specimens.
This set of guidelines, distilling many years of research to optimize molecular testing in lung cancer, is obviously only the beginning of a new approach to standardize testing for individualized therapy. Large-scale genomic studies through The Cancer Genome Atlas (TCGA) and other groups undoubtedly will identify several additional molecular targets for therapy. With further advances in molecularly targeted therapies, the number of targets to be tested will only expand incrementally.
It is likely that multiplex testing for a large set of molecular markers will soon become a reality in the clinic.
Wednesday, September 26, 2012
BY Peter S. Hammerman, MD, PhD
The management of lung adenocarcinoma, the most common type of non-small cell lung cancer (NSCLC) has evolved dramatically over the last decade due to the ability to identify subsets of patients who are likely to benefit from targeted therapies. The best examples of this modern approach are the use of erlotinib for patients with Epidermal Growth Factor Receptor (EGFR) mutations and crizotinib for individuals with fusions of the Anaplastic Lymphoma Kinase (ALK) gene. These targeted therapies, when used to treat individuals with these specific genetic alterations, lead to dramatically improved response rates as compared with conventional chemotherapy with far less associated toxicity. Tumor genotyping studies for EGFR, ALK and a number of other important genes have now become the standard of care for patients with lung adenocarcinoma, and new targeted therapeutic strategies continue to be identified in this disease.
In contrast to lung adenocarcinoma, targeted agents have not yet been shown to be successful in the treatment of squamous cell lung cancer, the second most common type of NSCLC. This has been largely due to a lack of knowledge of the genomic alterations that drive these tumors, leading to an inability to devise targeted therapeutic approaches for this disease. However, recent work by The Cancer Genome Atlas (TCGA) Network has greatly added to our knowledge of this disease.
TCGA is a joint NCI/NHGRI-funded initiative that has taken on the challenge of deeply studying over 20 tumor types using cutting-edge genomic technology. Squamous cell lung cancer was selected as a priority project, along with glioblastoma multiforme and serous ovarian cancer given the morbidity and mortality associated with these diseases.
In a recent publication, TCGA reports DNA and RNA sequencing, gene expression, copy number, methylation, and micro-RNA analysis of 178 squamous cell lung cancers. This is the largest study undertaken to date of squamous cell lung carcinomas by several orders of magnitude and the first to analyze tumors using this number of analysis platforms.
One of the major findings from the TCGA Network is that the majority of squamous cell lung cancers harbor a genomic alteration in a gene that is a likely therapeutic target. The most promising of these are alterations of Fibroblast Growth Factor (FGFR) and Phosphatidyl-inositol-3 (PI3K) kinase families. Clinical activity of FGFR inhibitors has already been reported in this disease for patients with amplification of FGFR1. Other important observations were the overall complexity of squamous cell lung cancers which harbor nearly 400 mutations per tumor. Almost all tumors have disruptions in two key tumor suppressor genes (TP53 and CDKN2A) and many demonstrated dysregulation of genes controlling squamous cell differentiation or cellular responses to oxidative damage. A surprising result was the identification of inactivating mutations in the HLA-A gene, suggesting that lung cancers may undergo mutations which make them less immunogenic.
The data from the study have been made publically available to the scientific community via the TCGA website. This will undoubtedly be a useful resource for investigators wishing to examine other genes and pathways in detail.
This work is one of several large genomic studies of lung cancer published recently which demonstrate the power of next-generation sequencing technologies. Further pre-clinical and clinical evaluation of altered genes in lung cancer will be essential to realize the full potential of these datasets and to continue to improve targeted treatment approaches.
Peter S. Hammerman, MD, PhD, a member of The Cancer Genome Atlas Research Network, is a medical oncologist at Dana-Farber Cancer Institute and an Instructor in Medicine at Harvard Medical School. He was on the Writing Committee of the TCGA lung cancer report.
Additional Comments from Ramaswamy Govindan, MD, OT Clinical Advisory Editor for Oncology and Co-chair of The Cancer Genome Atlas Project’s Lung Cancer Disease Working Group:
As Dr. Hammerman points out, tools and technologies that have evolved over the past decades now enable us to look at the complex genomic landscape of cancer cells as never before. Over the next several months, we plan to complete comprehensive genomic analyses of 1,000 patients with lung adenocarcinoma and squamous cell carcinoma. This research will hopefully unearth not only some new targets for therapy but also yield new information about cancer biology. The major take-home point from the TCGA study is that targeted therapies may soon be available for patients with squamous NSCLC.
Tuesday, February 22, 2011
BY CLIFFORD A. HUDIS, MD
For the past century or longer the conventional view has been that wide and careful removal of solid tumors was required for cure. In breast cancer this view was challenged by the series of trials led by the NSABP showing that the modified radical mastectomy was no worse than breast-conserving surgery. Clearly, some microscopic metastatic disease was left behind after both surgical procedures, but increasingly effective systemic adjuvant therapies were able to eradicate or control at least some of this, and, in any case, the extent of local surgery did not change this burden.
Said more plainly, the chances for a long life without distant recurrence were not different with more versus less radical surgery.
If the extent of breast surgery itself is not critical to the cure of breast cancer it is appropriate to ask about the functional role of axillary dissection. This local therapy causes some of the more troubling long-term consequences of breast cancer including decreased range of motion in the shoulder, increased risk of infection, risk of lymphedema, and pain.
In this context, the results of the ACOSOG Z0011 study, in the February 16th issue of JAMA, are provocative and important.
Patients with small (but typical) breast cancers, mostly hormone receptor positive, were treated with limited excision (and planned radiation therapy) and subjected to sentinel node biopsy. If they were found to have one or two nodes with involvement using conventional testing, they were randomized to no further axillary surgery or to axillary dissection.
The possible omission of a full axillary dissection following the discovery of positive sentinel nodes was bold and considered radical--if not harmful--by some potential investigators, limiting potential participation. Indeed, the study was not completed in terms of planned accrual, but the results in the nearly 900 patients randomized are none-the-less compelling, because if anything they run somewhat counter to expectations.
Furthermore, given what has been seen thus far it is highly unlikely that completion of the trial would meaningfully change the results.
About a quarter of patients who went on to complete axillary dissection had positive nodes. This suggests that about a quarter of the patients who did NOT have dissection harbored positive nodes. Despite this increased tumor burden in the axilla, there were very few axillary recurrences in either randomized arm and no difference in the small number of local and regional recurrences.
Similarly there were no discernable differences in disease-free or overall survival. In this context it is important to acknowledge the recent report by Weaver et al of the NSABP B-32 study. Here, small numbers of presumably malignant cells in the sentinel node were poor prognostic features. The critical issue, however, is whether their removal actually changes their impact--Z-0011 suggests not.
For medical oncologists, these results suggest that for patients with good-prognosis tumors treated with modern adjuvant therapy and radiation, it is not necessary to remove small numbers of involved axillary nodes to obtain an excellent outcome.
Critical Concept: Difference Between Prognosis & Prediction
Whether this holds up over the longest term remains to be seen, but in the meantime this highlights a critical concept: The difference between prognosis and prediction.
Putting aside the quality of local control, for most of our careers medical oncologists have used poor prognosis, as indicated by involved nodes, to select patients for more “aggressive” (read as chemotherapy) adjuvant treatment. In a sense we were assuming an even effect of chemotherapy such that with higher risk the benefits would outweigh its risks.
However, we don’t do that with trastuzumab or hormone therapy. Instead, for these targeted therapies we look for biological predictors of response (HER2, ER) and plan treatment accordingly and, to a degree, independently of risk (prognosis).
With the development of genomic and other predictors of chemotherapy sensitivity we may be liberated from reliance on node status as a surrogate for chemotherapy benefit. If so, then medical oncologists might be able to make systemic treatment decisions based on biology rather than anatomy.
If our surgical colleagues can demonstrate, as suggested by Z-0011, that local control is unaffected by the extent of local therapy (at least in a subset of low-risk patients), then we can offer as, or more, effective therapy at lesser total toxicity cost.
This is a move in the right direction.
CLIFFORD A. HUDIS, MD, is Chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center and Professor of Medicine at Weill Medical College of Cornell University; as well as Co-Chair of the Breast Committee of Cancer and Leukemia Group B.