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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_398"
                     title="ASCO GI: Gene Test, Nodes Predict Colon CA Recurrence Risk (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18301?impressionId=1265785812895"
                     
      &lt;p&gt;ORLANDO  --  An extended nodal examination and gene array test show promise for identifying patients at high risk of colorectal cancer recurrence in stage II disease, researchers reported at the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;Across the range of recurrence scores, examination of at least 12 nodes was associated with about a 5% absolute decrease in the three-year risk of recurrence in resected stage II colon cancers, compared with the same recurrence score and examination of fewer nodes.&lt;/p&gt;
&lt;p&gt;Noting limitations of other tests and biomarkers developed to evaluate recurrence risk, the gene expression-derived recurrence score &quot;has a real chance to make its way into the clinical decision algorithm,&quot; said David Kerr, MD, of the University of Oxford in England.&lt;/p&gt;
&lt;p&gt;Both recurrence score and number of nodes examined were independent predictors of recurrence risk, but investigators found no association or interaction between the two parameters of risk assessment.&lt;/p&gt;
&lt;p&gt;&quot;The test gives us more information about individual patients about the likelihood of the cancer returning,&quot; said Kerr, who was an investigator in the study. &quot;I think the quality of the science underpinning it, the size of the sample, and the compelling statistics all combine to make this a potential winner.&quot;&lt;/p&gt;
&lt;p&gt;Another study reported at the meeting showed few tumor-related genetic characteristics to distinguish stage II colon cancer from stage III.&lt;/p&gt;
&lt;p&gt;Both studies involved use a 12-gene assay (Oncotype DX) validated for predicting recurrence risk in stage II colon cancer. Investigators in the QUASAR validation study used data from the trial to evaluate the prognostic value of nodal assessment combined with other parameters, including the 12-gene assay.&lt;/p&gt;
&lt;p&gt;The National Comprehensive Cancer Network (NCCN) clinical guidelines for stage II colon cancer include number of nodes examined as a prognostic factor, Richard Gray, PhD, of the University of Birmingham in England, and colleagues noted in a poster presentation.&lt;/p&gt;
&lt;p&gt;Records for 657 stage II patients randomized to surgery alone showed that the median number of nodes examined was 10, including fewer than six nodes in 19% of patients and &amp;#8805;12 nodes in 37%. Risk of recurrence was more closely associated with examination of fewer than eight nodes versus more (HR 1.77, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) than with a cutoff point of 12 nodes (HR 1.38, &lt;em&gt;P&lt;/em&gt;=0.065). &lt;/p&gt;
&lt;p&gt;More nodes were examined in later than earlier years, the investigators found.&lt;/p&gt;
&lt;p&gt;In a model that included recurrence score derived from the gene assay and the 12-node threshold recommended by NCCN, both factors proved to be independent predictors of recurrence risk (&lt;em&gt;P&lt;/em&gt;=0.01, &lt;em&gt;P&lt;/em&gt;=0.05). Similar results emerged from models that incorporated mismatch repair (or microsatellite instability) and T stage.&lt;/p&gt;
&lt;p&gt;Across the range of recurrence scores, examination of &amp;#8805;12 nodes was associated with a 3% to 7% lower risk of recurrence compared with examination of fewer nodes (about 5% overall). The investigators concluded that both parameters should be included in assessment of recurrence risk after surgery for stage II colon cancer.&lt;/p&gt;
&lt;p&gt;The second study examined the 12-gene assay&apos;s ability to distinguish stage II from stage III colon cancer. Investigators evaluated the assay, pathologic markers, and expression of 375 different genes in 634 patients with stage II disease and 844 with stage III colon cancer.&lt;/p&gt;
&lt;p&gt;The data showed minimal differences in gene expression between the two stages of colon cancer.&lt;/p&gt;
&lt;p&gt;Five of the 375 genes differed significantly in their expression in stage II versus stage III cancer (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05). Two tumor characteristics differed by stage, as stage II colon cancer was more likely to be mismatch repair-deficient (&lt;em&gt;P&lt;/em&gt;=0.04) and have mucinous histology (&lt;em&gt;P&lt;/em&gt;=0.007).&lt;/p&gt;
&lt;p&gt;The data also showed significant interaction of grade and stage (&lt;em&gt;P&lt;/em&gt;=0.005), and borderline significance for interactions of stage with T-stage, mismatch repair, and mucinous histology, reflecting prognostic value in stage II but not stage III disease.&lt;/p&gt;
&lt;p&gt;Overall, investigators in this second study found a &quot;striking similarity between stages for the recurrence score and the vast majority of genes analyzed.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The studies were supported by Genomic Health.&lt;/p&gt;&lt;p&gt;Investigators in the studies included employees of Genomic Health.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_461"
                     title="Limited Benefit Seen in CML Drug, FDA Says"
                     score="0.01"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/18390?impressionId=1265785812895"
                     
      &lt;p&gt;WASHINGTON  --  Chronic myeloid leukemia (CML) patients who are resistant to imatinib (Gleevec) had a low response rate to treatment with omacetaxine (Omapro), according to Food and Drug Administration (FDA) reviewers.&lt;/p&gt;

&lt;p&gt;The FDA released its assessment of omacetaxine, made by ChemGenex Pharmaceuticals, in preparation for a meeting of an outside panel of oncology experts who will recommend whether the agency should approve the drug for imanitib-resistant CML patients with a Bcr-Abl T3151 mutation.&lt;/p&gt;
    &lt;p&gt;That meeting, original scheduled for Wednesday, was postponed when the federal government closed most Washington area offices because of snow. An FDA spokesman said no new date has been set.&lt;/p&gt;


&lt;p&gt;The agency does not have to follow the advice of its advisory panels, but it usually does.&lt;/p&gt;
&lt;p&gt;The Oncologic Drugs Advisory Committee will look at data from manufacturer ChemGenex&apos;s lone trial, which tested the safety and efficacy of subcutaneously administered omacetaxine in the target population.&lt;/p&gt;
&lt;p&gt;The trial divided 66 patients into disease stage cohorts of &quot;chronic phase,&quot; &quot;accelerated phase,&quot; or &quot;blast phase,&quot; and gave them 1.25 mg/m&lt;sup&gt;2&lt;/sup&gt; subcutaneous omacetaxine twice daily for 14 days every 28 days until hematologic response for induction therapy.&lt;/p&gt;
&lt;p&gt;If a patient achieved a complete hematologic response, hematologic improvement, or any cytogenetic response, the patient was transitioned to a maintenance does twice daily for seven days every 28 days.&lt;/p&gt;
&lt;p&gt;Researchers found: &lt;ul&gt; &lt;li&gt;For the chronic phase cohort of 40 patients, the major cytogenetic response rate was 15%, and the median duration of response was 7.7 months. &lt;/li&gt; &lt;li&gt;After a mean of nine months, 86% of the 49 chronic patients who were no longer controlling their diseases with imatinib had achieved a complete hematological response. &lt;/li&gt; &lt;li&gt;For the &quot;accelerated phase&quot; cohort of 16 patients, the major cytogenetic response rate was 6%, and the complete hematological response rate was 31%, with a median of duration of response of 22 weeks. &lt;/li&gt; &lt;li&gt;No patients responded in the more severe &quot;blast&quot; group, indicating omacetaxine works best among patients who are not as sick.&lt;/li&gt; &lt;li&gt;Overall, about 27% of patients achieved a major cytogenetic response, defined as absence of Bcr-Abl mutation in at least 35% of cells. About 18% of the patients had achieved a complete cytogenetic response, defined as all cells appearing to have lost the Bcr-Abl mutation.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;&quot;The response rate observed in the efficacy study was low,&quot; FDA reviewers concluded in documents released in advance of Wednesday&apos;s meeting.&lt;/p&gt;
&lt;p&gt;However, ChemGenex researchers said, &quot;These results demonstrate that omacetaxine is an effective and durable therapy with rapid onset of action for CML patients with the Bcr-Abl T315I mutation.&quot;&lt;/p&gt;
&lt;p&gt;The most common adverse events in the trial were thrombocytopenia, anemia, diarrhea, and neutropenia.&lt;/p&gt;
&lt;p&gt;The FDA reviewers cited a number of concerns with the ChemGenex study, noting that the company planned to enroll 100 patients but submitted efficacy data from only 66, and then continued to enroll additional patients after the prespecified data cutoff.&lt;/p&gt;
&lt;p&gt;Also, the reviewers said there is no commercially available test to detect the T3151 mutation. And, although it was a requirement of the study that the patients have a confirmed T3151 mutation, the mutation status of 35% of the patients in the trial was not confirmed.&lt;/p&gt;
&lt;p&gt;There are currently no approved drugs that have been found to be effective at treating CML patients with the T315I mutation.&lt;/p&gt;
&lt;p&gt;&quot;Omacetaxine offers an important therapeutic option for the treatment of CML patients who have the T315I mutation, a population that has a clear unmet medical need and no proven treatment options,&quot; ChemGenex researchers wrote in the company&apos;s briefing document.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_452"
                     title="Study Backs Late Cardiotoxicity of Childhood Cancer Treatment (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/HematologyOncology/OtherCancers/tb/18384?impressionId=1265785812895"
                     
      A childhood cancer survivor&apos;s risk of dying from cardiovascular causes rises with the dose of radiation his heart received during treatment, researchers in France and the U.K. affirmed.&lt;br&gt;
&lt;br&gt;Those whose hearts were exposed had a 60% higher risk of cardiovascular death than the general population, even at a dose of 1 Gy (95% CI 20% to 250%), according to Florent de Vathaire, PhD, of L&apos;Institut National de la Sant&amp;#233; et de la Recherche M&amp;#233;dicale in Paris, and colleagues.&lt;br&gt;
&lt;br&gt;The risk jumped to 12.5-fold for a cumulative radiation dose to the heart of 5 to 14.9 Gy, and to 14.9-fold for a dose of more than 15 Gy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 for trend), the researchers reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The notion that exposing the heart to radiation increases the risk of cardiovascular disease and death is not surprising, according to an accompanying editorial.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;However, this study examined cardiovascular mortality effects of both the dose of radiation and the dose of anthracyclines given to childhood cancer victims in the same cohort.&lt;/p&gt;
&lt;p&gt;That&apos;s something previous studies haven&apos;t done, according to editorialists Steven E. Lipshultz, MD, of the University of Miami and Holtz Children&apos;s Hospital in Miami, and M. Jacob Adams, MD, MPH, of the University of Rochester, N.Y.&lt;/p&gt;
&lt;p&gt;&quot;These are pretty profound findings,&quot; Lipshultz told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;These are the exact concerns we&apos;ve had based on careful subclinical assessments of how the heart in these survivors has been working.&quot;&lt;/p&gt;
&lt;p&gt;His group was one of the first to report that survivors of childhood cancer faced not only acute cardiotoxicity from treatment, but also late cardiac effects.&lt;/p&gt;
&lt;p&gt;As more effective treatment for childhood cancers came into play, the dramatic jump in survival rates  --  from less than 50% in the mid-1970s to 80% today  --  yielded a large enough population of survivors to make chronic issues from treatment apparent, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;&quot;It appears that for some of these survivors we have substituted one fatal disease of childhood  --  cancer  --  for another fatal disease of early adult life,&quot; he said.&lt;/p&gt;
&lt;p&gt;de Vathaire&apos;s group studied a cohort of 4,122 French and British children diagnosed with childhood solid cancer between 1942 and 1986 and who survived at least five years.&lt;/p&gt;
&lt;p&gt;Over an average of 27 years of follow-up, they were at 8.3-fold higher risk of dying from any cause compared with the general populations in France and the U.K. (95% CI 7.6 to 9.0).&lt;/p&gt;
&lt;p&gt;The majority of these excess deaths occurred early after diagnosis, five to nine years afterward in this analysis  --  in which all patients survived to five years.&lt;/p&gt;
&lt;p&gt;Based on just 32 deaths from cardiovascular diseases in the cohort, the childhood cancer survivors experienced five times the cardiovascular mortality (95% CI 3.3 to 6.7) expected from the general population (1.7% cumulative at 35 years versus 0.3%).&lt;/p&gt;
&lt;p&gt;This elevation in risk was similar to that seen in large studies from the U.S. and Nordic countries, suggesting generalizability of the results, Lipshultz said.&lt;/p&gt;
&lt;p&gt;Radiation therapy also conferred a 5.0-fold elevation in risk of cardiovascular disease-related death (95% CI 1.2 to 21.4).&lt;/p&gt;
&lt;p&gt;Like radiation, a higher cumulative dose of anthracycline chemotherapy also increased risk of dying from cardiac diseases, compared with the general population (RR 4.4 for a dose over 360 mg/m&lt;sup&gt;2&lt;/sup&gt;, 95% CI 1.3 to 15.3).&lt;/p&gt;
&lt;p&gt;However, radiotherapy and chemotherapy did not appear to interact for cardiovascular mortality (&lt;em&gt;P&lt;/em&gt;=0.4).&lt;/p&gt;
&lt;p&gt;Notably, the vinca alkaloids were also significantly linked to cardiovascular disease-related death risk among childhood cancer survivors, even after adjustment for sex, treatment period, age at diagnosis, follow-up, and all other treatment modalities (RR 3.6, 95% CI 1.0 to 12.9).&lt;/p&gt;
&lt;p&gt;Currently, guidelines support regular long-term cardiovascular screening for childhood cancer survivors who received anthracycline-based chemotherapy but provide little to no direction for those treated with nonanthracycline chemotherapy or radiation, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;These results suggested all three groups should be getting cardiac follow-up, he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;However, because other research has suggested that these individual treatments affect the heart in different ways, such as diastolic rather than systolic dysfunction with radiotherapy, screening modalities may need to account for this as well, he said.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that cardiovascular disease was probably under-reported as a cause of death in the cohort.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, 15 of the deaths classified as results of cancer as the principal cause had cardiovascular diseases as the immediate cause,&quot; they wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the Ligue Nationale Contre le Cancer; the Programme Hospitalier de Recherche Clinique; the Agence Fran&amp;#231;aise de S&amp;#233;curit&amp;#233; Sanitaire et Produit de Sant&amp;#233;; Electricit&amp;#233; de France; the Wyeth Foundation for childhood and adolescent health; and a grant from the Foundation of France.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;The editorialists reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_451"
                     title="Sentinel Nodes Predict Spread in Oral Cancer (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/HematologyOncology/OtherCancers/tb/18367?impressionId=1265785812895"
                     
      &lt;p&gt;In early oral squamous cell carcinoma, a sentinel node biopsy correctly predicted an absence of lymphatic metastasis in all but 4% of patients, researchers said.&lt;/p&gt;
&lt;p&gt;For T1 and T2 lesions that were clinically node-negative, the procedure  --  combined with additional sectioning and immunohistochemistry  --  yielded a negative predictive value of 96%, according to Francisco Civantos Jr., MD, of the University of Miami, and colleagues.&lt;/p&gt;
&lt;p&gt;For T1 lesions, the value was 100%, while for T2 cancers it was 94%, the researchers reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The finding may position the procedure as an intermediate option between watchful waiting and selective neck dissection, the researchers said, asserting that it&apos;s now &quot;reasonable&quot; to conduct a head-to-head trial of sentinel node biopsy and neck dissection.&lt;/p&gt;
&lt;p&gt;The procedure has significantly increased the sensitivity for detecting lymphatic metastasis in melanoma and breast cancer patients, Civantos and colleagues noted.&lt;/p&gt;
&lt;p&gt;But in oral cancer, many surgeons prefer a completion neck dissection, they added, despite the &quot;measurable morbidity&quot; that&apos;s associated with the procedure. On the other hand, because of that morbidity, other specialists prefer watchful waiting and elective neck irradiation.&lt;/p&gt;
&lt;p&gt;To investigate the issue, Civantos and colleagues conducted a multicenter trial in which patients with early invasive oral cancers were treated with both procedures  --  a sentinel node biopsy, followed by completion selective neck dissection.&lt;/p&gt;
&lt;p&gt;The primary goal was to see if a negative hematoxylin and eosin finding on the sentinel node biopsy accurately predicted the negativity of the other cervical lymph nodes removed in the neck dissection.&lt;/p&gt;
&lt;p&gt;All told, 140 patients qualified and had the dual procedures, the researchers reported.&lt;/p&gt;
&lt;p&gt;The sentinel nodes were identified using a radioactive gamma probe. The primary tumor was removed transorally, followed by the sentinel node biopsy through a small incision within the area of the planned incision for the neck dissection.&lt;/p&gt;
&lt;p&gt;Staining of the sentinel nodes at the various trial sites resulted in 106 that were negative. Of those, 100 were also negative by hematoxylin and eosin staining of the neck dissection specimens.&lt;/p&gt;
&lt;p&gt;That yielded a negative predictive value of 94%, the researchers said.&lt;/p&gt;
&lt;p&gt;Additional step sectioning and immunohistochemistry at a central pathology lab increased the negative predictive value to 96%, they said.&lt;/p&gt;
&lt;p&gt;Both findings were significant, they reported, with a one-sided &lt;em&gt;P&lt;/em&gt;-value of &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001.&lt;/p&gt;
&lt;p&gt;One limitation of the study, the researchers noted, is that the dual procedures may have interfered with each other, in that sentinel lymph biopsy might have changed the way the neck dissection was performed or the other way around.&lt;/p&gt;
&lt;p&gt;But that &quot;may actually lead to underestimation of the accuracy of this technique,&quot; they said, since the neck dissections were guided by information gleaned from nuclear imaging and the gamma probe used in the sentinel node procedure.&lt;/p&gt;
&lt;p&gt;The study was also limited, the researchers said, because many surgeons involved were only moderately experienced and none was experienced &quot;at levels currently considered appropriate for surgeons caring for breast cancer or melanoma.&quot;&lt;/p&gt;
&lt;p&gt;Nonetheless, they said, the negative predictive value found in the study was &quot;higher than anticipated for a multi-institutional setting with relatively inexperienced surgeons.&quot;&lt;/p&gt;
&lt;p&gt;They added that only a clinical trial in which outcomes after a negative sentinel node biopsy are simply observed for several years would yield a true negative predictive value for the procedure.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the National Cancer Institute.&lt;/p&gt;&lt;p&gt;Civantos reported no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_450"
                     title="SSRI and Tamoxifen Increase Mortality Risk (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/18376?impressionId=1265785812895"
                     
      Overlapping use of tamoxifen and the antidepressant paroxetine (Paxil) significantly increases the risk of breast cancer mortality, data from a large cohort of breast cancer patients showed.&lt;br&gt;
&lt;br&gt;The excess breast-cancer mortality risk ranged as high as 91%, depending on the duration of simultaneous use, researchers reported online in &lt;em&gt;BMJ.&lt;/em&gt;&lt;br&gt;
&lt;br&gt;Women taking other antidepressants with tamoxifen, including other selective serotonin reuptake inhibitors (SSRIs), did not have an increased risk of breast cancer death.&lt;br&gt;
&lt;br&gt;&quot;We estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 patients so treated; the risk with more extensive overlap would be greater,&quot; David Juurlink, MD, PhD, of Sunnybrook Health Sciences Center in Toronto, and colleagues concluded.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;The findings add to an accumulation of evidence suggesting that inhibition of the cytochrome P450 2D6 isozyme (CYP2D6) may adversely affect outcomes in breast cancer patients taking tamoxifen. CYP2D6 is the principle catalyst for converting tamoxifen into endoxifen, a metabolite with 100-fold greater affinity for the estrogen receptor.&lt;/p&gt;
&lt;p&gt;Multiple studies have shown that women who have a poor-metabolizer phenotype have lower levels of endoxifen, as do women treated with drugs that inhibit CYP2D6.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, in patients who receive tamoxifen in addition to a CYP2D6 inhibitor, endoxifen concentrations vary inversely with the degree of CYP2D6 inhibition,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Paroxetine is used to treat depression and vasomotor symptoms in breast cancer patients treated with tamoxifen. Paroxetine is not the only SSRI antidepressant used by breast cancer patients, but it is the only SSRI that irreversibly inhibits CYP2D6.&lt;/p&gt;
&lt;p&gt;Whether the metabolic effects of CYP2D6 inhibition translated into adverse breast cancer outcomes had not been determined.&lt;/p&gt;
&lt;p&gt;To examine the issue, Juurlink and colleagues compared prescribing data with clinical records of 24,430 breast cancer patients, ages 66 and older, who initiated tamoxifen therapy from 1993 to 2005. Of those, 7,500 also received an antidepressant.&lt;/p&gt;
&lt;p&gt;Ultimately, the investigators narrowed the study population to 2,430 women who took a single SSRI during tamoxifen therapy. The most commonly prescribed SSRI was paroxetine (25.9%), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15%), fluoxetine (10.4%), and fluvoxamine (7.2%).&lt;/p&gt;
&lt;p&gt;During a mean follow-up of 2.38 years, 1,074 patients died, including 374 breast cancer deaths.&lt;/p&gt;
&lt;p&gt;The analysis showed an increased risk of breast cancer death only among women taking paroxetine.&lt;/p&gt;
&lt;p&gt;The breast cancer mortality risk increased with the duration of concomitant use of paroxetine and tamoxifen. As the duration of therapeutic overlap increased from 25%, to 50%, to 75% of time on tamoxifen, the excess risk of breast cancer death increased from 24%, to 54%, to 91%.&lt;/p&gt;
&lt;p&gt;Investigators repeated the analysis, using death from any cause. Overlapping treatment with tamoxifen and paroxetine led to an increased mortality risk of 13%, 28%, and 46% as the duration of overlap increased from 25% to 75%.&lt;/p&gt;
&lt;p&gt;The results suggest clear implications for use of SSRIs in breast cancer patients on tamoxifen, Frank Andersohn, MD, and Stefan Willich, MD, of Charite University in Berlin, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;&quot;The straightforward answer is to avoid prescribing strong CYP2D6-inhibiting SSRIs (such as paroxetine or fluoxetine) for women with breast cancer who are prescribed tamoxifen, and to consider instead drugs with low potential to inhibit CYP2D6 (such as citalopram or venlafaxine),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;For women who are already taking a potent inhibitor of CYP2D6, doctors should consider switching to a drug that does not inhibit the enzyme, they added. However, any switch should be accomplished gradually, as abrupt discontinuation of an antidepressant confers risk, as well, they noted.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Co-author Kathleen Pritchard disclosed relationships with sanofi-aventis, AstraZeneca, Roche, Pfizer, Ortho-Biotech, YM Biosciences, Novartis, Abraxis, Amgen, GlaxoSmithKline, Bristol Myers Squibb, and Roche&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>