		The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.

		Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

		Upon completion, participants should be able to:

			Describe new preventive options and treatments for cancer patients

			Identify options for individualizing the treatment for cancer patients

			Review new evidence to facilitate survivorship and supportive care for cancer patients

		Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hours. 

CBRN credit is not accepted by the Michigan and Utah State licensing boards.

		Dannemiller is approved as a provider of nurse practitioner continuing education by the American Association of Nurse Practitioners: AANP Provider Number 090419. The program was planned in accordance with AANP CE Standards and Policies and AANP Commercial Support Standards. It provides 1.0 contact hours of continuing education (which includes 0.0 hours of pharmacology).

		The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.

		To resolve identified/potential conflicts of interest, the educational content was fully reviewed by a member of the Dannemiller Clinical Content Review Committee, Gloria Herrera, RN, MSN, FNP-BC, who has no financial relationships with commercial interests. The resulting certified activity was found to provide educational content that is current, evidence based and commercially balanced. *Note: Please list the reviewer(s) name and disclosure provided by Dannemiller (physician, RD, and/or NP)

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		This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by FDA. The faculty have been asked to disclose this information when presented. The opinions expressed in the educational activity are those of the faculty. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Further, participants should appraise the information presented critically and are encouraged to consult appropriate resources for any product or device mentioned in this activity.

			Read the articles in this section in its entirety.

			Complete and submit the CE posttest and activity evaluation.

		This activity is provided free of charge to participants.

		Radiation Therapy for DCIS Does Not Increase Risk of Cardiovascular Disease

	Women with ductal carcinoma in situ (DCIS) treated with radiation therapy had no increased risk of cardiovascular disease (CVD) compared with women in the general population or women with DCIS treated with surgery, according to results of a study in The Netherlands. The study was presented at the 2013 Breast Cancer Symposium, held September 7-9, 2013 in San Francisco, California. Abstract 58

	“Doctors have been worried about late effects of breast radiation therapy, particularly cardiovascular disease,” said Naomi B. Boekel, MSc, the study’s lead author and a PhD student at The Netherlands Cancer Institute in Amsterdam. “Our findings suggest that routine radiation therapy for women with DCIS does not appear to increase the risk of developing cardiovascular disease later in life.”

	The researchers collected data on 10,468 women in The Netherlands diagnosed with DCIS before age 75 years between 1989 and 2004. About 71% of the women were treated with surgery alone (43% had a mastectomy and the rest underwent lumpectomy) and 28% were treated with surgery and radiotherapy. The median follow-up was 10 years; 19% of the women were followed for 15 years or more. The study compared the risk of CVD in women treated with radiotherapy with that of the general population of Dutch women and to different treatment groups of women with DCIS.

	Compared with the general population, women with DCIS had a similar risk of dying from any cause and a 30% lower risk of dying of CVD. No difference was found in the risk of CVD in women treated with radiotherapy versus surgery alone (8% of patients treated with surgery plus radiation were diagnosed with CVD vs 9% treated with surgery alone). Likewise, no significant differences in the risk of CVD were observed in patients who received left-side radiotherapy (7%) versus right-side (8%).

	The findings are important in light of current concerns about overtreating patients with DCIS, said Boekel. Radiation therapy following lumpectomy for DCIS approximately halves the rate of cancer recurrence in the same breast. However, previous studies in breast and other cancers have shown that radiation to the heart region can increase the long-term risk of CVD, and in recent years, radiation therapy protocols have been adjusted to decrease exposure of the heart to radiation.

	The slightly lower risk of dying from CVD in women with DCIS might be the result of those women being more health conscious than the general population, so that they underwent breast cancer screening or adopted a healthier lifestyle after DCIS diagnosis, Boekel said. In addition, factors such as education, socioeconomic status, and conflicting risk factors between CVD and DCIS (eg, age at menopause) may also play a role. “Studies with longer follow-up after breast radiation therapy are needed before definitive conclusions about cardiovascular disease risk can be drawn,” she said.

		T-DM1 in Previously Treated HER2+ Metastatic Breast Cancer

	An analysis of the T-PAS expanded access study of trastuzumab emtansine (T-DM1) in previously treated HER2+ metastatic breast cancer (MBC) confirmed existing information on the safety of the combination, and observed significant clinical activity in a patient population that averaged seven prior therapies. The analysis was presented at the 2013 Breast Cancer Symposium, held September 7-9 in San Francisco, California. Abstract 166

	The study enrolled 215 HER2+ (IHC 3+ or FISH/CISH+) patients with locally advanced or MBC and left ventricular ejection fraction (LVEF) ≥50%. All of the patients, who received 3.6 mg/kg of T-DM1 every 3 weeks, had already been treated with an anthracycline and a taxane as well as capecitabine or 5-FU and ≥2 HER2-directed agents (including trastuzumab and lapatinib).

	At baseline, the median LVEF was 60%, and 50% of patients had investigator-reported cardiovascular disease. The median follow-up was 5.9 months; median T-DM1 duration was 5.0 months, with 15.8% receiving >18 cycles. Objective response rate, as assessed by investigators on day 1 of every cycle, was 25.6%.

	The rate of ≥grade 3 adverse events was 43.7%, and rate of serious adverse events of any grade was 18.1%. The most common ≥ grade 3 adverse events were thrombocytopenia (7.9%), fatigue (4.7%), and increased aspartate aminotransferase and anemia (3.7%). Cardiac dysfunction (primarily asymptomatic decreases in LVEF) of any grade occurred in eight patients and of ≥ grade 3 in four patients. There were no ≥ grade 3 bleeding events.

		Breast Cancer Patients Prefer Subcutaneous Trastuzumab

	Women with HER2-positive early breast cancer favor subcutaneous over intravenous (IV) administration of trastuzumab (Herceptin), according to the results of the PrefHer study (

	Xavier Pivot, MD, with CHU Jean Minjoz in Besançon, France, and coworkers elsewhere randomized subjects to receive four cycles of 600-mg fixed-dose subcutaneous adjuvant trastuzumab administered via a single-use injection device or handheld syringe, followed by four cycles of IV trastuzumab, or the reverse sequence. Treatment regimens containing IV trastuzumab are the standard of care for patients with HER2-positive breast cancer.

	In the 596-patient, phase III HANNAH trial, subcutaneous trastuzumab demonstrated a pharmacokinetic profile and efficacy that was noninferior to IV administration, with a similar safety profile.

	The PrefHer study included women with HER2- positive primary invasive breast adenocarcinoma and evidence of residual, locally recurrent, or metastatic disease after completion of surgery and chemotherapy.

Articles

CE lesson worth 1.0 contact hour that is intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

Clinical Insights: October 2013

		Psychosocial Benefits Derived From Patient Website Chronicling

	A program to help patients with breast cancer to create personal websites, so that they can write about their experiences and communicate more effectively with their social network, yielded statistically significant improvement in depressive symptoms, positive mood, and life appreciation among its participants, establishing a basis for a larger study of the intervention. (

	To test their hypothesis that women trained in maintaining a personal website would reap psychological benefits from such engagement, researchers—led by Annette Stanton, PhD, professor in the Department of Psychology at UCLA and a member of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center in Los Angeles, California&mdash;designed Project Connect Online (PCO), which comprises a 3-hour, hands-on, small-group workshop guiding patients in the construction of a personal website, follow-up phone communication to facilitate use of the tool, and a take-home manual.

	During their 3-hour session, participants each created their own websites, using a standard design template offering several functions, including a journal blog with functionality for photos, a “How You Can Help” page where participants could suggest actions for visitors to the website (eg, providing a meal or written notes), and instructions for visitors to post messages and subscribe to automatic updates.

	To test the efficacy of this approach, researchers recruited participants from community-based medical oncology practices focusing on breast cancer. Enrollees (n = 88) were randomly assigned to receive PCO (n = 46) or a waiting-list control (n = 42). The average age of participants was 56, with their breast cancer diagnosis occurring, on average, >5 years previously.

	All patients were treated with ibrutinib 420 mg per day in 28-day cycles.

	Ibrutinib was safe and well tolerated. The most common adverse events were grades 1 and 2 diarrhea, rash, arthralgia, cramps, mouth sores, and fatigue. Hematologic adverse events were rare, and no treatment-related drug discontinuations were reported. Two deaths occurred, both unrelated to the study drug.

	Both groups were assessed at baseline and 6 months later, using such standard measures of psychological status as the Center for Epidemiologic Studies Depression Scale, the Profile of Mood States, the Impact of Event-Intrusion subscale (a cancer-related outcome measure), and two subscales of the Posttraumatic Growth Inventory: Appreciation of Life and Relating to Others. The control group received standard medical care and was offered PCO after the 6-month assessment had been completed.

	Baseline assessments did not differ significantly between the PCO group and controls, although the status of women in current medical treatment was somewhat worse, researchers noted.

	At the 6-month assessment, researchers reported significant improvement in depressive symptoms, positive mood, and life appreciation among patients using PCO, noting that the magnitude of the effect size for all statistically significant effects was moderate to large. The PCO benefit was not significant, however, for measures of negative mood, perceived strengthened relationships, or intrusive thoughts.

	Women in active medical treatment—most of whom had metastatic disease&mdash;reported more depressive symptoms at the 6-month mark (

 = .04), and for this subgroup, the PCO intervention was especially beneficial (

	The researchers added that this preliminary trial was the first of its kind, with high potential for dissemination. Topics for further research include whether the greater benefit observed in patients currently being treated and/or those with advanced disease is reproducible, an analysis of any cultural variation in effects, and a comparison of this intervention with other online or personal approaches.

	Project Connect Online (PCO), a program to help breast cancer patients create a personal website so they can write about their experiences and communicate with others, showed promising effects, including improvement in depressive symptoms, positive mood, and life appreciation. Interestingly, women with metastatic disease and/or those undergoing chemotherapy benefited the most from PCO. Clinically this is concordant, as patients who have the greatest disease burden or are undergoing active chemotherapy are among the patients who have the most need for support.

	In rural Kansas where I practice, cancer patients are often isolated and don’t have easy access to services like support groups and other educational programs. The PCO intervention is ideal for cancer patients who suffer from isolation. I think we all would agree that cancer patients who stay socially connected and have a good support system do better both physically and emotionally.

	A challenge I perceive with the PCO intervention is funding and long-term implementation and maintenance of such a project. Perhaps larger tests of PCO with larger samples of patients and positive findings would strengthen support for this program and help elicit other sources of funding to assure the success of PCO.

		HER2-Targeted Therapies May Provide Simple, Nontoxic Therapeutic Alternative

	With the approval of sipuleucel-T for prostate cancer, the notion of utilizing vaccines in the fight against various tumors has garnered considerable interest. Yet HER2-targeted vaccines for breast cancer have been in development for several years. Now, clinical trials of these vaccines are starting to yield very promising data, although work still needs to be done to determine which patients will benefit the most from this type of therapy.

	At the 12th International Congress on the Future of Breast Cancer, held July 18-20, Elizabeth A. Mittendorf, MD, PhD, an assistant professor in the department of Surgical Oncology in the division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, discussed the development of these vaccines, where they stand, and the challenges that lie ahead in terms of determining how efficacious this new class of drugs might be.

	While sipuleucel-T is a dendritic cell vaccine, the vaccines currently in development for breast cancer are peptide vaccines, which are proteinbased vaccines that incorporate one or more short or long amino acid sequences as tumor antigens, which are then combined with a vaccine adjuvant. Mittendorf said that a peptide vaccine will stimulate a peptide-specific immune response.

	The peptide vaccine that has been investigated the most thoroughly at this point is E75, also known by its brand name Neuvax. E75 is a 9-amino acid peptide derived from the extracellular domain of HER2. “Our group has hypothesized that cancer vaccines, such as E75 vaccine, will be more effective in minimal disease or adjuvant setting,” Mittendorf said.

	patients—which Mittendorf noted is the largest number of patients enrolled in an adjuvant vaccine trial to date&mdash;with histologically confirmed breast cancer who were nodepositive or high-risk node-negative and had any level of HER2 were randomized into either the vaccination group (n = 108) or the control group (n = 79).

	The majority of patients (81%) did experience grade 1 maximal toxicity, usually involving redness at the injection site. The majority of patients (71%) also experienced grade 1 systemic toxicity, usually involving bone pain or flu-like symptoms. Overall, the vaccine was relatively well-tolerated.

Clinical Insights: September 2013

		Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. 

RNs outside California must verify with their licensing agency for approval of this course.

Highlights From the Year's Largest Oncology Conference, Featuring Peer Perspectives From Oncology Nurses

	More than 25,000 oncology professionals representing a broad range of specialties attended the 49th Annual Meeting of the American Society of Clinical Oncology, held May 31-June 4, 2013 in Chicago, Illinois. With a theme of “Building Bridges to Conquer Cancer,” experts presented the latest cutting-edge, multidisciplinary developments in oncology care. In this month’s continuing education activity, oncology nurses comment on the practice implications of some of the noteworthy research presented at the meeting.

	Low-dose weekly paclitaxel is as effective as and has fewer side effects than the standard biweekly schedule for patients with early-stage breast cancer, according to the results of a phase III study presented at the 2013 ASCO Annual Meeting. Abstract CRA1008.

	Paclitaxel is typically prescribed in either weekly or biweekly regimens. This is the first study to formally compare the two dosing schedules. The low-dose weekly administration of the chemotherapy agent paclitaxel resulted in equal disease-free survival (DFS) in patients with early-stage breast cancer when compared with biweekly administration of the drug, and although each dosing regimen resulted in a different set of side effects, the weekly dosing schedule appeared to offer a slightly more favorable side-effect profile.

	“It’s important to give these drugs in an optimal way,” said G. Thomas Budd, MD, a medical oncologist at the Cleveland Clinic in Cleveland, Ohio, and lead author of the study. Budd noted that paclitaxel used to be given in higher doses every 3 weeks in the treatment of breast cancer until studies showed that the weekly and biweekly schedules in this study yielded superior results.

	In this phase III trial, 3294 patients with node-positive or high-risk node-negative operable breast cancer first received treatment with one of three different regimens of doxorubicin and cyclophosphamide, after which they were randomized to receive either a low-dose regimen of paclitaxel weekly for 12 weeks or a standard-dose regimen of paclitaxel every 2 weeks for 12 weeks with pegfilgrastim support.

	As of April 2013, DFS was essentially the same with both schedules of paclitaxel (hazard ratio = 1.05; 95% CI, 0.89-1.25).

	“It appears from these data that either way of giving paclitaxel produces a similar outcome,” Budd said. “An investigator and a patient or a doctor and a patient could choose either one of these schedules.”

	The rate of any grade 3/4 toxicity was similar across the two arms, occurring in 36% of patients receiving the biweekly regimen and 35% of patients receiving the weekly regimen. However, researchers found that the different dosing schedules were characterized by different types of side effects of different severities. Allergic reactions were more common in the biweekly dose (1.4%) compared with the lower dose (0.6%), as were symptoms of bone and muscle pain (11% vs 3%, respectively).

	Neurologic toxicity was also more frequent in the biweekly dose of paclitaxel compared with the low-dose regimen (17% vs 10%, respectively), but Budd noted that patients received six cycles of the biweekly regimen instead of the standard four cycles for the purposes of scientific comparison, which may have slightly affected the frequency of these side effects.

	The rate of hematologic toxicity was higher in the weekly-dose arm (17%) than the biweekly-dose arm (6%), as was the rate of leukopenia (6% vs 1%, respectively) and neutrophils (11% vs 2%, respectively). However, the rate of neutropenic fever was low in both groups (0.4% vs 0.1%, respectively) and the difference was not statistically significant (P = .29). Budd explained that the higher rates of hematologic toxicity in the weekly schedule could have been a result of ascertainment bias, since patients had toxicities measured on a weekly basis rather than the biweekly basis of the other study arm.

	“In this study, the weekly schedule seemed to be less toxic for most patients,” Budd said.

	Women with early sentinel lymph nodepositive breast cancer achieve as much of a disease-free and survival benefit from axillary radiotherapy (ART) as they do from axillary lymph node dissection (ALND) with significantly less risk of lymphedema, according to clinical trial results presented at the American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract LBA1001

	The findings of the phase III AMAROS trial align with the gradual move away from reliance upon surgery in managing early breast cancer and are likely to be embraced in the United States by patients and oncologists alike, research leaders said in discussing the data.

	Andrew D. Seidman, MD, an attending physician for the Breast Cancer Medicine Service at Memorial Sloan- Kettering Cancer Center in New York, said the study would influence treatment for women with early breast cancer, a group that makes up approximately 80% of the 230,000 new cases diagnosed in the United States annually. “This is going to represent a new option for patients, other than having full clearance of their axillary lymph nodes,” said Seidman, who served as an ASCO commentator on the study.

	The study comparing the dosing schedules of weekly or biweekly administration of paclitaxel for early-stage breast cancer patients is very exciting. Results of this study show that the weekly dosing and biweekly dosing of paclitaxel are both effective and resulted in equal disease-free survival in patients with early-stage breast cancer.

	For an oncologist and patient, this study is helpful in determining what regimen option is going to be best for the patient, while not having to compromise the efficacy of this drug. For instance, where we practice in rural western Kansas, many patients find the distance traveled for treatment to be a barrier— be it cost, or travel time, etc. Some patients with early-stage breast cancer can afford the slight increased toxicity of paclitaxel so that they only have to travel every other week.

	On the other hand, it is helpful to know that some women may not be able to tolerate the larger biweekly dose of paclitaxel but may benefit and tolerate the once-weekly administration of this drug. For these patients, the only other option would have been to not administer paclitaxel at all due to concern over adverse side effects and tolerability. Either way of administering paclitaxel gives the patient and treating oncologist options for efficacious treatment that does not compromise chance of cure.

CE Activity Worth 1.0 Contact Hour Featuring Highlights From the Year's Largest Oncology Conference and Peer Perspectives From Oncology Nurses.


ASCO 2013: Building Bridges to Conquer Cancer

	Ibrutinib was well tolerated and highly effective in eradicating tumor cells in both treatment-naïve and relapsed/refractory patients with chronic lymphocytic leukemia (CLL) in an ongoing phase II study reported at the 2013 Annual Meeting of the American Association for Cancer Research. The drug dramatically reduced disease burden in the lymph nodes, blood, spleen, and bone marrow, and responses were durable. Further, correlative studies confirmed on-target effects of ibrutinib demonstrating sustained inhibition of B-cell receptor signaling and NF-kappa B signaling in both peripheral blood and lymph nodes.

	“The degree of tumor reduction achieved by oncedaily oral ibrutinib was impressive. Within just 2 months, we have seen patients with more than 90% reduction of lymph node tumor burden,” said lead author Adrian Wiestner, MD, PhD, of the National Institutes of Health in Bethesda, Maryland.

	Ibrutinib is a selective inhibitor of Bruton’s tyrosine kinase (BTK), an element of the B-cell receptor signaling pathway implicated in the evolution of CLL. This study confirms the activity of ibrutinib reported earlier this year at the American Society of Hematology meeting, particularly in patients with deletions of the 17p chromosome, who are known to be difficult to treat, Wiestner commented.

	The phase II single-center trial included two cohorts of patients with CLL who required treatment: elderly patients over age 65 years (n=24; 8 treatment- naïve; 16 relapsed/refractory) and those with deletion of chromosome 17p (n=29; 15 treatmentnaïve; 14 relapsed/refractory).

	The drug achieved rapid disease control in all anatomic sites at 6 months; 95% of patients achieved at least a 73% reduction in lymph node disease burden, as well as a reduction in splenomegaly (median reduction, 55%). In 26 patients with an available bone marrow biopsy, ibrutinib reduced tumor infiltration by CLL cells by 82%. Absolute lymphocyte count was reduced by a median of 62%. According to standard response criteria for CLL, the rate of partial response was 52%. At 12 months, the estimated event-free survival was 94%.

Adult Blood and Marrow Transplantation Division

	Chronic lymphocytic leukemia (CLL) is the second most common adult leukemia, and it is estimated in the United States that over 4500 people will die from the disease this year.

 While many patients can be initially managed with a “watch and wait” approach, patients with advancedstage or high-risk disease typically have a poor response to standard chemotherapy.

	Targeted therapies have been shown to be effective in a variety of malignancies, and in some cases have become the standard of care, such as the tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, has been shown to be well tolerated and effective in reducing tumor burden in the blood and lymph nodes of patients with CLL. This phase II study included elderly CLL patients with a 17p deletion, both treatment-naïve or relapsed/refractory. The initial dramatic response is encouraging, and it will be interesting to see the duration of response as well as any chronic side effects from the drug.

	Future clinical trials can focus on not only the use of ibrutinib as a single agent, but also in combination with other targeted therapies, possibly eliminating the need for toxic chemotherapy. Based on these results, for patients with CLL, ibrutinib can offer a chance for disease control and the potential for improved quality of life.

	1. (2013) SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia. 

http://seer.cancer.gov/statfacts/html/clyl.html

		Adoptive T-Cell Therapy Combined With Vaccine Shows Promise in Difficult-to-Treat Ovarian Cancer

	A two-step immunotherapy approach consisting of adoptive T-cell therapy and a dendritic cell vaccine has shown activity in a phase I advanced ovarian cancer clinical trial. The results were presented at the American Association for Cancer Research (AACR) Annual Meeting 2013 held April 6-10 in Washington, DC, by Lana Kandalaft, PharmD, PhD, assistant professor and director of Clinical Development and Operations at the Ovarian Cancer Research Center at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

	All patients had recurrent, progressive, stage 3 or 4 ovarian cancer. Of 31 patients treated with the vaccine, 19 (61%) showed a clinical benefit from the combination immunotherapy. Eight of the 19 patients had no measurable disease at the end of the trial but remained on maintenance vaccine therapy. One patient remains disease-free after 42 months in complete remission.

	Ovarian cancer is the fifth leading cause of death from cancer among women. It remains difficult to treat partly because it is typically diagnosed at an advanced stage, and there is a high unmet need for better, more durable treatment of advanced ovarian cancer. The 5-year survival rate for stage 4 invasive epithelial ovarian cancer is approximately 18%.

	The new immunotherapy requires a sample of the patient’s tumor taken at the time of surgery in order to create a personalized vaccine. The researchers isolate immune cells called dendritic cells from the tumor sample. Six of the patients in the trial received an initial version of the vaccine, and the subsequent 25 received an optimized version developed at the Penn Ovarian Cancer Research Center. According to Kandalaft, the team is continuing to work to improve the vaccine.

	As long as the tumor tissue from the patient is resected at time of surgery in a sterile manner and preserved while the tissue is still alive using cryogenics, the vaccine can be created, according to Kandalaft.

	Eleven patients in total were treated with the combination of dendritic cell vaccine and adoptive T-cell therapy. All of these patients initially received the vaccine but still had residual disease and went on to receive adoptive T-cell therapy. The patients’ T-cells were removed from peripheral blood samples, expanded in the laboratory, and then reinjected into the patient. Seven of the 11 patients had stable disease, and one had a complete response.

	Analyses showed that because the patients’ immune systems were already primed by the dendritic cell vaccine to attach tumor cells, the subsequent adoptive T-cell transfer magnified the immune response further.

Clinical Insights: June, 2013

		The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the art care for those with or at risk for cancer.

		Neoadjuvant Regimen May Not Require Chemotherapy in Some HER2-Positive Breast Cancer Patients

	Some HER2-positive breast cancer patients may be able to receive targeted neoadjuvant therapy with lapatinib and trastuzumab without chemotherapy, according to findings of a study by the Translational Breast Cancer Research Consortium (TBCRC) published online April 8, 2013 in the 

	In this phase II, single-arm, multicenter study, 64 HER2-positive women with invasive stage IIIII disease received a nonchemotherapy regimen of trastuzumab (4 mg/kg loading dose, followed by 2 mg/kg once weekly) and lapatinib (1000 mg once daily) over 12 weeks. Patients with estrogenreceptor (ER)— or progesterone-receptor (PR)– positive tumors also received one daily dose of letrozole (2.5 mg).

	Tumors were biopsied on four occasions: baseline, weeks 2 and 8, and at the end of study treatment. The pathologic complete response (pCR) rate was determined by whether all invasive tumor had disappeared from the breast (ypT

), the most common definition employed in other neoadjuvant studies, according to the researchers. The other study goal was the pathologic response rate, defined by investigators as pCR plus residual invasive disease of ≤1 cm (ypT

	The nonchemotherapy regimen achieved a pCR of 27%; pCR in the ER-positive and ER-negative subsets was 21% and 36%, respectively. The researchers noted that even when using a stricter definition of pCR (no residual invasive cancer in the breast or axilla [ypT

]), the pCR was 22%. The overall pathologic response rate was 49%; in ER-positive and ER-negative patients, it was 54% and 40%, respectively.

	Disease progressed in just two patients—each with ER- and PR-negative tumors&mdash;during the treatment period, and the regimen was generally well tolerated, with 6% of patients discontinuing treatment due to adverse events. Diarrhea (grades 1-2) was the most common toxicity, reported in 63% of patients, followed by skin rash (grades 1-2) in 55% of participants. Other events included fatigue (32%) and nausea (31%).

	Mothaffar F. Rimawi, MD, of Baylor College of Medicine, Houston, Texas, the lead study site, and colleagues noted that achieving this rate of pCR with targeted therapy but without chemotherapy suggests a subset of patients with HER2-positive breast cancer may exist who do not need chemotherapy. The biomarkers needed to identify this subset are currently being studied in tumor samples from this trial.

		Nurse Perspective on Neoadjuvant Treatment

	Phase II research suggesting a neoadjuvant regimen that may not require chemotherapy in some HER2-positive breast cancer patients is very interesting and thought-provoking.

	A subset of HER2-positive patients may have excellent neoadjuvant outcomes with the administration of trastuzumab and lapatinib, and the addition of letrozole in estrogen/progesterone-positive cancer. This would spare some patients the toxic side effects of chemotherapy that make cancer treatment difficult and complicated.

	Certainly, this research is hypothesis-provoking, and additional research will need to be conducted comparing this particular regimen to current standard regimens that include chemotherapy. Additionally, research is needed to determine biomarkers to accurately identify this subset of patients who are eligible for this treatment option. Protocols for monitoring of progress and primary endpoints with this targeted neoadjuvant therapy will need to be determined as well.

		Radiotherapy Increases Risk of Heart Disease in Some Women With Breast Cancer

	While radiotherapy can be an effective treatment for early-stage breast cancer, incidental irradiation of the heart during treatment may increase the risk of developing ischemic heart disease, according to a recent study (

. 2013;368(11):987-998). The researchers explained that the risk is small for most women, however, and that their study should actually help physicians identify patients for whom radiotherapy is most appropriate.

	“We carried out this work because doctors could not reliably estimate the risk of heart disease in women treated with radiotherapy for breast cancer. Doctors can now estimate the risk and know that in most cases it will be very small, so that they can reassure their patients. In addition, the few women for whom radiotherapy poses undue risk can now be identified, so that alternative techniques can be considered,” said lead author Sarah Darby, PhD, University of Oxford, in a statement.

	Darby and colleagues’ population-based analysis looked at major coronary events (defined as myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women in Sweden and Denmark who received radiotherapy for breast cancer between 1958 and 2001. Of those women, 963 had experienced major coronary events, whereas the other 1205 served as controls. The researchers estimated the mean radiation doses to the whole heart and to the left anterior descending coronary artery from information on the patient’s radiotherapy chart.

	The researchers found that the overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03-27.72), with mean doses of 6.6 Gy for women with tumors in the left breast and 2.9 Gy for tumors in the right breast. They noted that exposure at 1 Gy is enough to raise the risk of ischemic heart disease.

	In the study, the rate of major coronary events increased by 7.4% for each increase of 1 Gy of radiation that the heart received (95% CI, 2.9-14.5; P <.001). When the authors grouped women based on whether the mean radiation dose to the heart was less than 2 Gy, 2 to 4 Gy, 5 to 9 Gy, or ≥10 Gy, the percentage increases of major coronary events compared with the estimated rate if the dose of radiation had been 0 were 10%, 30%, 40%, and 116%, respectively.

	According to the researchers, no significant difference was observed in the percentage increase per Gy when accounting for matching factors used in the selection of controls, tumor characteristics, or cancer treatments that were given in addition to radiotherapy. A higher rate of major coronary events was observed in women with cardiac risk factors compared with those who did not have such risk factors, but the percentage rate increase in the rate of major coronary events per Gy was similar for women with or without those risk factors at the time they were diagnosed with breast cancer.

	The authors noted that a limitation of the study was the fact that individual computed tomography (CT)-based information on radiotherapy was not available for the women studied because they were treated prior to when three-dimensional CT-based planning was being implemented for radiotherapy. However, using data from CT-based planning scans, they found that the patient-to-patient variation in mean radiation dose to the heart was minimal.

. 2013;368(11):1055-1056), Javid Moslehi, MD, co-director of the Cardio-Oncology Program at Brigham & Women’s Hospital and instructor in the Department of Medicine at Harvard Medical School/Dana- Farber Cancer Institute, wrote that this study may represent “just the tip of the iceberg” in the link between cardiac issues and radiotherapy, since radiation therapy has been associated with other cardiac conditions that were not included in this study, including pericardial disease, peripheral vascular disease, cardiomyopathy, valvular dysfunction, and arrhythmias.

	“Given the widespread use of radiation therapy in the treatment of breast cancer, and the continually expanding arsenal of novel therapies, the current study calls for greater collaboration between oncologists and cardiologists,” Moslehi wrote. “An important lesson for the oncologist may be that the time to address concerns about cardiovascular ‘survivorship’ is at the time of cancer diagnosis and before treatment rather than after completion of therapy.”

Clinical Insights: May, 2013

	Shortening the course of androgen blockade (AB) therapy from 36 months to 18 months when combined with radiation therapy does not appear to compromise outcomes in patients with high-risk prostate cancer, according to results of a randomized, multicenter, phase III study reported at the 4th Annual Genitourinary Symposium held February 14-16, 2013, in Orlando, Florida (Abstract 3).

	The study found that both overall survival (OS) and disease-specific survival (DSS) were similar in patients who received 36 or 18 months of treatment.

	Hormone therapy is associated with uncomfortable and disturbing side effects that negatively impact quality of life. These include hot flashes, decreased libido, impotence, and fatigue.

	“A long list of side effects makes the lives of most of our patients quite miserable,” commented lead author Abdenour Nabid, MD, associate professor at Centre Hospitalier de Universitaire de Sherbrooke in Sherbrooke, Canada. “A shorter course could reduce the quantity and intensity of its unpleasant side effects as well as treatment costs. We hope these results will convince doctors that they can stop hormone therapy after 1.5 years instead of 2 to 3 years.”

	The study enrolled 630 patients with node-negative, high-risk prostate cancer treated with radiotherapy to the pelvic area and prostate bed. They were randomized to either 36 months (n = 310) or 18 months (n = 320) of AB therapy (bicalutamide 50 mg for 1 month plus goserelin 10.8 mg every 3 months) given before, during, and after radiation.

	Patient characteristics were well balanced between the two arms, with a median age of 71 years, median PSA of >20 ng/mL, and a median Gleason score of >7. The majority of patients had stage T3-4 disease.

	At a median follow-up of 77 months, the two groups had no significant difference in biochemical failure, metastasis, bone-only metastasis, and cause of death. Mortality rates were 22.9% (71 patients) in the longerduration hormone therapy arm versus 23.8% (76 patients) in the shorter-duration arm. Of 147 deaths, 116 were deemed unrelated to prostate cancer.

	Five-year OS was 92.1% in the longer-duration arm versus 86.8% in the shorter-duration arm, and 10-year OS was 63.6% versus 63.2%, respectively. Five-year DSS was 97.6% and 96.4%, respectively, and 10-year DSS rates were 87.2% in both arms.

		Nurse Perspective on Shortened Hormonal Therapy

	This study potentially represents a very meaningful advance in the treatment of localized prostate cancer. As pointed out, the symptom burden for patients undergoing the current bimodality standard of care is quite significant.

	Improved survival data in most cases can be the motivating factor for patients and their healthcare providers to consider the benefits of longer treatment courses to outweigh the risks. This study’s results, if borne out in the review process, are very compelling in the context of presenting a 50% reduction in treatment duration while still delivering efficacious care.

	In this case, “more” appears not to be significantly better than “less.” The fact that this study did not involve the introduction of a new androgen blocker or other type of agent or a new radiation treatment technique could represent other gains.

	In the context of affordability of care or quality of life, advantages to such new and/or extended treatment approaches can be somewhat offset by significantly higher costs to the patient and/or the insurer or increased side effects. With respect to the latter concern, it would be interesting to see data on the quality of-life comparison between the two treatment arms. While this study’s results will no doubt be welcome news, one could wonder why this potential treatment “threshold” was not previously revealed in the typical dose-/time-escalating process of determining the length of treatment for the current standard of care.

		Aggressive Prostate Cancer Risks Higher

	A large, retrospective study has found that high-risk prostate cancer that can only be detected through prostatespecific antigen (PSA) testing is more likely to occur among men over the age of 75 and in African Americans, according to research reported at the 2013 Genitourinary (GU) Cancers Symposium (Abstract 50).

	The findings come amid a continuing debate over the merits of PSA screening, particularly after the US Preventive Services Task Force (USPSTF) recommended against routine screening for the general male population last May based on the finding that the harms of overdiagnosis outweigh the potential benefits of screening.

	The results of this study suggest that PSA testing can be useful in identifying an aggressive form of prostate cancer in asymptomatic men with early disease that is not detectable by physical exam or other tests.

	In their population-based study, researchers from the University of Rochester Medical Center in New York determined that elderly men account for approximately 40% of all cases of high-risk, PSA-detected prostate cancer and are 9.4 times more likely than men under the age of 50 to be high risk. African-American men of any age are more likely than white men to have high-risk disease.

	In addition, intermediate-risk prostate cancer was more likely to occur among elderly and African- American men, the study found.

	“To the best of our knowledge, this is the largest analysis exclusively consisting of PSA-detected prostate cancer (T1cN0M0 disease). We found that men age 75 and older and African Americans are at highest risk of intermediate or high-risk disease,” stated lead author Hong Zhang, MD, PhD, an associate professor of Radiation Oncology at the University of Rochester, during a press conference before the symposium where the results were announced.

CE lesson worth 1.0 contact hour that is focused on supportive care and research from the 2013 Genitourinary and Gastrointestinal Cancers Symposia.

Clinical Insights: March/April, 2013

	2012 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS)

	The mental toll and stress of a breast cancer diagnosis might factor into the cognitive impairment experienced during chemotherapy treatment, commonly referred to as “chemo brain.” At the 35th Annual San Antonio Breast Cancer Symposium, Bernadine Cimprich, PhD, RN, presented data suggesting that pretreatment neurocognitive compromise and fatigue contribute to cognitive issues formerly associated solely with chemotherapy.

	“Our [previous] work and the work of others has shown that cognitive complaints and deficits have occurred even before chemotherapy, so these [problems] could not be attributed to the treatment,” said Cimprich, who is an associate professor emerita at the University of Michigan School of Nursing in Ann Arbor. “It’s important to find solutions because even subtle cognitive changes can have a considerable negative impact on a person’s functioning and quality of life. And, further, concern over ‘chemo brain’ may result in patient reluctance to accept life-saving therapy.”

	In their latest study, Cimprich and her colleagues analyzed neurocognitive responses in 66 women with localized breast cancer (stages 0-IIIa), as well as in 32 healthy controls. Patients were receiving either an anthracyline-based adjuvant chemotherapy combination (n = 29) or radiotherapy (n = 37).

	Cimprich explained the design of the trial: “Functional magnetic resonance imaging was used to directly test brain function while a woman was performing a working memory task in the scanner before adjuvant treatment and then 1 month after adjuvant treatment.”

	After each scan, patients self-reported on levels of cognitive functioning and fatigue.

	In both patient groups, pretreatment brain imaging revealed lower functioning versus the control arm in frontal regions of the brain that were necessary to the performance of the working memory task. The cognitive impairment was most severe in women awaiting chemotherapy. “The chemotherapy group actually had the lowest level of activation [before treatment] and [results] with the radiation group fell between the prechemotherapy and the controls,” said Cimprich.

	Cimprich said the study demonstrates the need for increased awareness of the vulnerability of women awaiting chemotherapy to cognitive problems related to worry and fatigue.

	Cimprich noted that the findings suggest that “chemo brain” might be an inappropriate term to describe cognitive problems in patients with cancer. 

		Nurse Perspective on Cognitive Impairment

Janice Famorca Tran, RN, MS, AOCNP®, CBCN®, ANP-C

	Cognitive impairment as a result of cancer treatment occurs in a majority of patients, with most patients experiencing improvement after treatment completes; however, for a subset of this population, the problem may persist.

	The presence of cognitive impairment, both in its severity and duration, can cause a significant amount of distress. The majority of studies have examined the effects of cancer treatment on cognitive impairment; however, the study performed by Cimprich and colleagues took a different approach in studying this relationship. They concluded that decreased brain function prior to treatment predicted lower levels of cognitive functioning and increased levels of fatigue. Additionally, the pre-chemotherapy group had higher levels of cognitive impairment compared to controls.

	These results suggest that feelings such as stress, worry, and anxiety about treatment and cancer may potentially contribute to increased cognitive impairment and fatigue. This study implicates the importance of pre-psychological screening of all cancer patients in order to identify high-risk patients so that appropriate interventions can be undertaken early in order to assist patients with this problem. These interventions may include emotional support by the nurse, professional counseling, patient involvement in peer support groups, and spiritual activities.

		Adjuvant Chemotherapy Improves Survival

	Adjuvant chemotherapy improved survival rates in women with isolated local or regional breast cancer recurrence, according to results from the CALOR trial presented by Stefan Aebi, MD, at the 2012 SABCS. Aebi, head of the division of Medical Oncology at Luzerner Kantonsspital in Luzern, Switzerland, said the greatest benefit was observed in patients with estrogen receptor (ER)—negative disease.

	Aebi and colleagues from the Breast International Group, the National Surgical Adjuvant Breast and Bowel Project, and the International Breast Cancer Study Group randomized 162 patients (median age, 56 years) with recurrent tumors to chemotherapy (n = 85) or no chemotherapy (n = 77). “The choice of chemotherapy was determined by the patient’s treating oncologist based on her prior therapy,” Aebi said. A minimum of four cycles of a multidrug chemotherapy regimen was recommended.

	Patients were evenly distributed between the two trial arms in terms of location of recurrence (breast, chest wall/mastectomy scar, or lymph nodes), ER status, and menopause status. Sixty-eight percent and 58% of patients in the control and treatment arms, respectively, had prior adjuvant chemotherapy. The median time between patient surgeries for primary and recurrent disease was 5 years in the treatment group and 6 years in the control group.

	At 4.9 years’ follow-up, the overall survival (OS) rate for patients receiving adjuvant chemotherapy was 88% versus 76% in the control arm (hazard ratio [HR] = 0.41; 95% CI, 0.19-0.89; 

 = .02). Five-year disease-free survival (DFS) rates were 69% and 57% with and without chemotherapy, respectively (HR = 0.59; 95% CI, 0.35-0.99; P = .046). The data remained statistically significant in statistical analyses controlling for recurrent disease location, ER-status, prior adjuvant chemotherapy, and interval between primary and recurrent surgeries.

	In women with ER-negative disease, 5-year DFS was 67% in the treatment arm versus 35% in the control group (HR = 0.32; 95% CI, 0.14-0.73; 

 = .007). Fiveyear OS in ER-negative patients was 79% with adjuvant chemotherapy versus 69% without (HR = 0.43; 95% CI, 0.15-1.24; 

	DFS at 5 years in patients with ER-positive recurrent tumors was 70% and 69%, respectively, with and without treatment (HR = 0.94; 95% CI, 0.47-1.89; 

 = .87). OS rates were 94% and 80%, respectively (HR = 0.40; 95% CI, 0.12-1.28; 

 = .12). Aebi commented that the ER-positive data are not yet mature. “When I say now that we found no statistically significant benefit in the ER-positive group, this does not mean that it will stay this way with further follow-up. We need to observe these patients for a longer period of time.”

	Regarding side effects, Aebi said nothing abnormal was observed in the treatment arm. “Toxicity-wise, we observed what is expected from these chemotherapies.”

CE lesson worth 1.0 contact hour that is focused on research from the 2012 American Society of Hematology Annual Meeting and the San Antonio Breast Cancer Symposium.

Clinical Insights: January/February, 2013

		Lapatinib Plus Trastuzumab Bests Solo Lapatinib in Metastatic Breast Cancer

	Investigators have documented a significant 4.5-month median overall survival advantage with lapatinib combined with trastuzumab versus lapatinib monotherapy in women with heavily pretreated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC).

	The findings are from an update of the phase III EGF104900 study (

. 2012;30(21):2585- 2592), which had found in an earlier analysis that combination therapy significantly improved progression-free survival (PFS), the primary endpoint (HR = 0.73; 93% CI, 0.57-0.93; 

	Overall, the data bolster the hypothesis that combining anti-HER2 agents “may optimize their use,” Kimberly L. Blackwell, MD, professor of Medicine and assistant professor of Radiation Oncology at Duke University Medical Center in Durham, North Carolina, and associates wrote.

	The updated analysis is based on data from January 2009 and includes all 291 patients with HER2-positive MBC who were randomized to lapatinib in tandem with trastuzumab or to lapatinib alone after their disease had progressed during prior trastuzumab-based therapy. The earlier PFS results were drawn from data available in June 2007.

	The updated analysis found that lapatanib plus trastuzumab continued to demonstrate superiority to lapatinib monotherapy in investigator-assessed PFS (HR = 0.74; 95% CI, 0.58-0.94; 

 = .011). In addition, the median OS was 14 months for combination therapy and 9.5 months for lapatinib alone (HR = 0.74; 95% CI, 0.57-0.97; 

	The data also showed a 10% improvement in absolute overall survival (OS) rate at 6 months and a 15% improvement at 12 months in the combination group versus the monotherapy group.

	Overall, 94% of patients who received combination therapy and 90% of patients who received monotherapy experienced adverse events.

	Blackwell et al pointed out that their findings corroborate preclinical data indicating that the lapatinib plus trastuzumab combination has synergistic antiproliferative activity.

	They also emphasized that “clinically relevant” OS improvement occurred even though more than half of women who were initially randomized to lapatinib monotherapy switched to combination therapy upon disease progression.

	Finally, they noted that the median 4.5-month survival advantage is on par with improvements that have been reported when trastuzumab is added to chemotherapy as frontline treatment for HER2-positive MBC.

	“Although the optimal setting for combining anti-HER2 agents is unknown, this strategy seems beneficial and may allow patients to omit chemotherapy for a period of time,” they said.

		Nurse Perspective on Lapatinib Plus Trastuzumab

	Women with metastatic breast cancer are facing many difficult choices these days. There are many new regimens which may be helpful, and new research often compares a known monotherapy regimen with a newer combination of drugs that may have a better outcome.

	This study also points out one of the serious issues that these women must deal with—adverse events. The review did not explicate what the adverse events were, or how serious they were, but it is difficult to experience many of them over and over. As one patient told me, “This will be the third time I have lost all my hair.”

	However, the improvement in overall survival and progression-free survival are significant, and should be considered. Patients with metastatic disease must make hard decisions, based on their personal situation and concerns, so the nurse needs to make certain that all choices are presented with all of the risks and benefits, and support the patient’s decision, whatever it may be.

		Meningioma Risk May Be Tied to Dental X-Rays

	New data suggest that dental x-rays obtained frequently at a young age may boost the risk of intracranial meningioma.

	“Although dental x-rays are an important tool in well-selected patients, efforts to moderate exposure to IR [ionizing radiation] to the head is likely to be of benefit to patients and healthcare providers alike,” Elizabeth B. Claus, MD, professor and director of Medical Research at Yale University School of Public Health, New Haven, Connecticut, and attending neurosurgeon at Brigham and Women’s Hospital in Boston, and her coauthors wrote (

	For their study, the investigators compared dental and therapeutic radiation histories in 1433 patients who had intracranial meningioma diagnosed when they were between 20 and 79 years of age with histories from 1350 healthy controls matched for age, sex, and state of residence.

Oncology Nursing News