<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_450"
                     title="SSRI and Tamoxifen Increase Mortality Risk (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/18376?impressionId=1265791119561"
                     
      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>
    <recommendedItem id="20100101_19_429"
                     title="Low-Dose Radiation in Breast Cancer Gets Support (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/18339?impressionId=1265791119561"
                     
      &lt;p&gt;About 40% of women in two large breast cancer radiotherapy trials reported being concerned about some aspect of body image over the five years following therapy, researchers said.&lt;/p&gt;
&lt;p&gt;But there was little difference between those in the standard therapy arms and those getting so-called hypofractionated regimens, according to Penelope Hopwood, MD, of the Institute of Cancer Research in Sutton, England, and colleagues.&lt;/p&gt;
&lt;p&gt;The finding is evidence that a lower overall radiation dose given in fewer but larger fractions does not increase adverse effects or worsen body image for most women, Hopwood and colleagues said online in &lt;em&gt;The Lancet Oncology&lt;/em&gt;&lt;em&gt;&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The researchers used data from quality-of-life substudies from the two randomized Standardisation of Breast Radiotherapy (START) trials, conducted concurrently in the U.K.&lt;/p&gt;
&lt;p&gt;The Start A trial compared a standard regimen  --  50 gray (Gy) delivered in five 2.0-Gy fractions weekly over five weeks  --  with two hypofractionated regimens.&lt;/p&gt;
&lt;p&gt;In the first test regimen, women were treated with 41.6 Gy in 13 fractions of 3.2 each over five weeks, with three fractions in one week and two the next. The other regimen followed the same schedule, but delivered 39 Gy in 13 fractions of 3.0 each.&lt;/p&gt;
&lt;p&gt;The Start B study was a noninferiority trial comparing the standard regimen with one that delivered 40 Gy in 15 fractions of 2.67 each over three weeks. In contrast to Start A, both regimens had five fractions per week.&lt;/p&gt;
&lt;p&gt;As part of the studies, the researchers enrolled 2,208 participants in a quality-of-life analysis that looked at adverse events and changes in body image over a five-year follow-up period.&lt;/p&gt;
&lt;p&gt;They found: &lt;ul&gt; &lt;li&gt;The most frequently reported adverse effects in women with breast-conserving surgery were breast hardness and overall change in breast appearance after radiotherapy  --  about 41% and 39%, respectively, at five years. &lt;/li&gt; &lt;li&gt;In all radiotherapy regimens, breast symptoms fell significantly (at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001) from baseline to 60 months, but there was no significant difference between regimens in either trial.&lt;/li&gt; &lt;li&gt;Compared with the standard regimen, adverse effects of radiotherapy tended to be lower for the 39 Gy regimen in trial A and the 40 Gy regimen in trial B, but rates were similar between the control regimen and the 41.6-Gy regimen in trial A. &lt;/li&gt; &lt;li&gt;The only significant difference from the 50-Gy regimen, however, was adverse change in skin appearance, which was lower for patients who received 39 Gy or 40 Gy. The hazard ratios were 0.63 and 0.76, respectively.&lt;/li&gt; &lt;li&gt;There was no significant difference in change in skin appearance between patients who got 41.6 Gy or 50 Gy in trial A. (The hazard ratio was 0.83, but the 95% confidence interval crossed unity.)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Overall, the findings &quot;strengthen evidence in favor of hypofractionated regimens, with a potential for fewer adverse effects on the normal breast tissues,&quot; the researchers concluded.&lt;/p&gt;
&lt;p&gt;The study&apos;s findings &quot;provide a strong foundation&quot; for more research into how patients experience radiotherapy, according to Julie Schnur, PhD, of Mount Sinai School of Medicine in New York City.&lt;/p&gt;
&lt;p&gt;Among areas that might be examined, she wrote in an accompanying editorial, are: &lt;ul&gt; &lt;li&gt;The acute treatment period, which &quot;presents unique challenges to women&quot;&lt;/li&gt; &lt;li&gt;How women view the treated breast specifically, rather than the body overall&lt;/li&gt; &lt;li&gt;The use of behavioral medicine approaches to enhance body image&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Schnur said the researchers showed &quot;a consideration of the patient&apos;s point of view that is too often absent.&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 study had support from Cancer Research UK, the U.K. Medical Research Council, and the U.K. Department of Health.&lt;/p&gt;&lt;p&gt;The authors declared 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_345"
                     title="FDA Okays Drug Combo for Advanced Breast Cancer"
                     score="0.01"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/18224?impressionId=1265791119561"
                     
      &lt;p&gt;The FDA has approved a combination of lapatinib (Tykerb) and letrozole (Femara) to treat hormone-positive and HER2-positive advanced breast cancer in postmenopausal women.&lt;/p&gt;
&lt;p&gt;The approval follows a company-sponsored study that found that women with HER2-positive disease who were taking the combination had survival rates more than double that of women on letrozole alone (35 weeks versus 13 weeks).&lt;/p&gt;
&lt;p&gt;Lapatinib is an oral kinase inhibitor that blocks the function of the HER2-positive protein. In 2007, it was approved in combination with capecitabine (Xeloda) to treat advanced HER2-positive breast cancer tumors in refractory disease. (See &lt;a href=&quot;http://www.medpagetoday.com/HematologyOncology/Chemotherapy/5247&quot; mce_href=&quot;http://www.medpagetoday.com/HematologyOncology/Chemotherapy/5247&quot; target=&quot;_blank&quot;&gt;FDA Okays Lapatinib (Tykerb) for Treatment-Resistant Breast Cancer&lt;/a&gt;).&lt;/p&gt;
&lt;p&gt;The FDA said the most commonly reported side effects of the lapatinib/letrozole combination were diarrhea, rash, nausea, and fatigue.&lt;/p&gt;
&lt;p&gt;Treatment with lapatinib has also been associated with decreased heart function, liver damage, and inflammation of lung tissue, the agency cautioned. It may also cause harm to the fetus if used in pregnant women.&lt;/p&gt;
&lt;p&gt;Richard Pazdur, MD, director of the FDA&apos;s office of oncology drug products, said in a prepared statement that the combination &quot;provides women being treated for advanced breast cancer with an important treatment option.&quot;&lt;/p&gt;
&lt;p&gt;Lapatinib is marketed by GlaxoSmithKline and letrozole by Novartis AG.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_333"
                     title="More Benefits of Targeting HER2 in Breast Cancer (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Oncology/BreastCancer/tb/18206?impressionId=1265791119561"
                     
      &lt;p&gt;The addition of trastuzumab (Herceptin) before and after surgery significantly improved event-free survival compared with neoadjuvant chemotherapy alone in women with HER2-positive locally advanced or inflammatory breast cancer, investigators in a multicenter European trial reported.&lt;/p&gt;
&lt;p&gt;Patients treated with trastuzumab had a 40% reduction in the hazard ratio for the composite endpoint of recurrence, progression, or death from any cause.&lt;/p&gt;
&lt;p&gt;&quot;Although locally advanced breast cancer is relatively infrequent in affluent countries compared with nonaffluent countries, it is still an area of medical need, especially in regions of the world where diagnosis tends to occur late for cultural or economic reasons,&quot; Luca Gianni, MD, of the National Cancer Institute in Milan, Italy, and colleagues wrote in the Jan. 30 issue of &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Neoadjuvant chemotherapy has a key role in the management of patients with locally advanced and inflammatory cancers. Anthracycline- and taxane-based regimens have produced high response rates and rates of breast-conserving surgery for patients with operable breast cancer, the authors wrote.&lt;/p&gt;
&lt;p&gt;About 35% of locally advanced and 40% of inflammatory breast cancers are associated with HER2 amplification or overexpression. Trastuzumab, which targets HER2, has demonstrated efficacy as monotherapy and in combination with chemotherapy for patients with HER2-positive metastatic and early operable breast cancer, the authors continued.&lt;/p&gt;
&lt;p&gt;Trastuzumab does not have specific approval for treatment of locally advanced or inflammatory breast cancer and has not been studied extensively for those indications. So the investigators designed the neoadjuvant Herceptin (NOAH) study to assess the efficacy of neoadjuvant chemotherapy plus trastuzumab followed by adjuvant trastuzumab.&lt;/p&gt;
&lt;p&gt;The randomized trial compared the regimen versus neoadjuvant chemotherapy alone in 235 patients with newly diagnosed HER2-positive locally advanced or inflammatory breast cancer.&lt;/p&gt;
&lt;p&gt;The investigators conducted a parallel observational study involving 99 patients with newly diagnosed HER2-negative locally advanced or inflammatory breast cancer. Those patients too were treated with chemotherapy alone, which consisted of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and 5-FU.&lt;/p&gt;
&lt;p&gt;The primary endpoint was event-free survival, defined as the time from randomization to disease recurrence or progression or death from any cause.&lt;/p&gt;
&lt;p&gt;After a median follow-up of 3.2 years, the three-year event-free survival was 71% in the trastuzumab arm and 56% in the patients who received chemotherapy without trastuzumab. The difference translated into an unadjusted hazard ratio of 0.59 (95% CI 0.38 to 0.90, &lt;em&gt;P&lt;/em&gt;=0.013).&lt;/p&gt;
&lt;p&gt;Regression analysis confirmed that treatment with trastuzumab was the only factor that significantly affected event-free survival, resulting in a hazard ratio of 0.58 compared with the chemotherapy-only arm (&lt;em&gt;P&lt;/em&gt;=0.126).&lt;/p&gt;
&lt;p&gt;Three-year overall survival was not significantly different between the treatment arms of HER2-positive patients but trended in favor of the trastuzumab arm (87% versus 79%). The authors noted that the 17% crossover to treatment with trastuzumab may have lessened the observed survival difference.&lt;/p&gt;
&lt;p&gt;The HER2-negative patients had a three-year event-free survival of 67% and overall survival of 86%.&lt;/p&gt;
&lt;p&gt;Rates and severity of noncardiac adverse events were similar in all three treatment groups, the authors reported. Fewer patients in the trastuzumab arm maintained normal left ventricular ejection fraction (LVEF) throughout the study, but most reductions in LVEF were grade 1 in severity. Two patients had grade 2 (asymptomatic) reductions in LVEF, and two had reversible grade 3 decreases.&lt;/p&gt;
&lt;p&gt;Gianni and colleagues acknowledged that the benefit in the trastuzumab arm could have occurred as a result of both neoadjuvant and adjuvant use of trastuzumab. However, the magnitude of the benefit (HR 0.59) was greater and the number needed to treat was lower compared with adjuvant trials of trastuzumab, Melanie D. Seal, MD, and Stephen K. Chia, MD, of the British Columbia Cancer Agency in Vancouver, wrote in a commentary.&lt;/p&gt;
&lt;p&gt;&quot;Adjuvant studies require thousands of women to show survival benefits, at high cost and often long follow-up,&quot; Seal and Chia wrote. &quot;Studies such as NOAH illustrate the benefits and potential of neoadjuvant trials and should challenge the dogma of our current strategies of therapeutic trials in early-stage breast cancer.&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 study was supported by F. Hoffmann-La Roche.&lt;/p&gt;&lt;p&gt;Gianni disclosed relationships with Roche, Genentech, GlaxoSmithKline, Wyeth, Novartis, Millennium, Biogen Idec, and Eisai. Co-author Jose Baselga disclosed relationships with Exelixis, Merck, Novartis, Roche, and GlaxoSmithKline. Co-author Andrea Feyereislova is a Roche employee. Co-author Claire Barton disclosed relationships with Roche, ONO Pharma, Cellact, Acadia, Michelangelo, BTG Ltd, Kuros Biosurgery, Micromet AG, Bioenvision, Norgine, Piramed, and GlaxoSmithKline.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_230"
                     title="Radiation Benefit of Digital Mammogram Not Clear (CME/CE)"
                     score="-0.001"
                     href="http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/18087?impressionId=1265791119561"
                     
      &lt;p&gt;Digital mammography exposes women to a lower radiation dose than standard film mammography, but digital imaging is likely to require more than four normal views in about 20% of women screened, according to a subset analysis of data from a study of almost 50,000 women.&lt;/p&gt;
&lt;p&gt;The mean glandular dose per view was 2.37 mGy for film mammography versus 1.86 mGy for full-field digital mammography, a difference of 22%, R. Edward Hendrick, PhD, of the University of Colorado-Denver, and colleagues reported in the February issue of the &lt;em&gt;American Journal of Roentgenology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;But only 12% of women screened with traditional mammography required more than four normal views compared with 21% of the women imaged with digital systems.&lt;/p&gt;
&lt;p&gt;When the need for additional views was factored in, they wrote, the difference in radiation exposure between the two modalities dropped to 17%, 4.14 mGy for digital versus 4.98 mGy for standard mammography.&lt;/p&gt;
&lt;p&gt;Furthermore, these differences were not standard  --  there was a wide variation across manufacturers. For example, the average mean glandular dose per view was 3.77 for Fischer digital versus 5.03 for Hologic Selenia, which was also the only manufacturer in which the digital dose was higher than the standard film dose.&lt;/p&gt;
&lt;p&gt;Doses were compared on a manufacturer basis  --  film mammography versus digital: &lt;ul&gt; &lt;li&gt;5.36 mGy for Fischer standard film versus 3.77 mGy for Fischer digital&lt;/li&gt; &lt;li&gt;4.02 mGy for Fugifilm standard film versus 4.45 mGy for Fugifilm digital&lt;/li&gt; &lt;li&gt;5.03 mGy for GE standard film versus 4.02 mGy for GE digital&lt;/li&gt; &lt;li&gt;5.01 mGy for Hologic CCD standard film versus 4.60 for Hologic CCD digital&lt;/li&gt; &lt;li&gt;4.24 mGy for Hologic Selenia versus 5.03 for Hologic Selenia digital &lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The analysis of parameters and radiation dose was culled from data collected by the American College of Radiology Imaging Network Digital Mammographic Imaging Screening (DMIST) trials, which enrolled 49,528 women from October 2001 through October 2003.&lt;/p&gt;
&lt;p&gt;The primary goal of DMIST was to compare the accuracy of the two technologies. The results, reported in 2005, found that digital mammography was superior for younger women and for women with dense breasts, but when results from all 50,000 women were considered there was no significant difference.&lt;/p&gt;
&lt;p&gt;This latest study was based on technical data compiled on 5,102 women of which 4,366 cases yielded &quot;clean&quot; data that were included in the analysis.&lt;/p&gt;
&lt;p&gt;The researchers did find a significant difference in the pressure each modality exerted on the breast. &quot;Mean compression force was 10.7 dN for screen-film mammography and 10.1 dN for full-field digital mammography (5.5% difference, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;There was also a 1.7% statistically significant difference in mean compressed breast thickness  --  5.3 cm for screen-film mammography versus 5.4 cm for digital.&lt;/p&gt;
&lt;p&gt;But the difference in breast compression, while statistically significant, was &quot;likely clinically insignificant,&quot; Hendrick and colleagues concluded.&lt;/p&gt;
&lt;p&gt;The authors noted that the study was limited by the advances in imaging technology  --  since the study was conducted, film manufacturers have introduced &quot;new screen-film combinations, such as double-sided screens and double-emulsion films that were not available during DMIST.&quot;&lt;/p&gt;
&lt;p&gt;For that reason, &quot;breast dose along with image quality and other parameters should be carefully compared between existing screen-film mammography and any new [digital] system being considered for integration into a breast imaging practice.&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 DMIST trial was supported by the National Cancer Institute and by the Lynn Safe Breast Cancer Research Foundation.&lt;/p&gt;&lt;p&gt;Hendrick disclosed that he is a consultant to GE Healthcare on digital breast tomosynthesis and other breast imaging projects not related to DMIST.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>