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Best Practices in breast cancer – October 2017 Vol 8

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Breast Cancer Management

Breast Cancer Treatment

Sharon S. Gentry, RN, MSN, AOCN, CBCN, ONN-CG
Breast Nurse Navigator
Novant Health Derrick L. Davis Cancer Center,
Winston-Salem, NC 

A treatment decision-making process by the patient begins once a breast cancer diagnosis is confirmed, and Byers states a navigator requires advanced clinical skills to support patients undergoing cancer treatment.1 A breast nurse navigator can perform patient-centered education on breast cancer type and possible treatment options using the inclusive pathology report, as well as be available during the disease trajectory to proactively guide the patient with additional education and support.2 Nurse navigators can improve communication among the healthcare team, expedite care, and ensure that the patient receives appropriate interventions throughout the care continuum.3 Upon diagnosis, many informed decisions need to be made, such as genetic assessment, surgical choice, possible neoadjuvant chemotherapy, and the possible future need for radiation therapy and systemic therapy with chemotherapy or endocrine treatment. A nurse navigator can expedite referrals to the appropriate healthcare members so a personalized approach can be consolidated for the patient based on the prognostic and predictive factors of the disease.

Several breast navigation practices provide positive testimony to placing a navigator at this transition point and support the Academy of Oncology Nurse & Patient Navigators (AONN+) metric from the Operations Management/Organizational Development/Health Economics domain that measures patient retention through navigation (Figure 1). Henrico Doctors’ Hospital in Virginia used a gap analysis to recognize the need for a nurse navigator to be placed earlier in the breast continuum and described this transition point as a major stimulus to keep patients in the system for further care.4 This change in navigation practice decreased the breast patient outmigration rate from 240 to 28 in 1 year. The financial impact to the system was $350,000 in billable services or procedures in 1 year because the navigator educated the patient on pathology results and followed up on further scheduling needs.

In 2011, by listening to the voice of the patient stating that breast nurse navigation was the reason they returned to the system after going out for a second opinion, Novant Health Derrick L. Davis Cancer Center published a report showing that the annual revenue captured from breast nurse navigation decreasing outmigration was $436,000.5 At that particular time, breast navigation started after the primary care physician had shared the diagnosis with the patient. In 2013, a system change placed a nurse navigator with the patient at the time of diagnosis with a breast radiologist, and the rate of outmigration decreased further and brought in $272,500 in revenue to the healthcare system.6 Figure 2 from the AONN+ domain Coordination of Care/Care Transitions addresses multidisciplinary communication with referrals to revenue-generating services, or downstream revenue, such as radiology, rehabilitation, palliative care, and tumor site-specific pre/rehab programs, which is also supported by the positioning of a nurse at the diagnostic transition point.

A focal point of interaction for the clinical trial engagement with the patient is also at the time of diagnosis, where the navigator can promote the introduction of a clinical trial. Holmes and colleagues employed a nurse navigator to educate patients about cancer, including possible clinical trial treatment options and logistics of care, as well as the community physicians about available clinical trials and completing trial documentation.7 Within 2 years, 86% of the eligible black patients were enrolled in at least 1 protocol, and the accrual of this population increased from 3% to 7% with involvement of the nurse navigator. In 2013, when Novant Health Derrick L. Davis Cancer Center placed a nurse navigator at the time of diagnosis, a primary objective was to promote clinical trial participation as each patient was evaluated for neoadjuvant chemotherapy.6 Within 1 year, clinical trial participation increased by 20.4% for eligible patients. This practice shows added value in navigation by using the metric from the AONN+ domain Coordination of Care/Care Transitions that addresses clinical trial referrals (Figure 3).

Once a breast cancer has been diagnosed, it is impor­tant for navigators to be aware that breast cancer is not a singular homogeneous disease. Its varied molecular nature causes it to be a collection of biologically discrete diseases that range from in situ (noninvasive, stage 0) to invasive (stage I-IV), with tissue subtypes of ductal, lobular, lymphoma, sarcomas, and others.8 Navigators need to be aware of advances in surgery, radiation therapy, chemotherapy, and hormone therapy to be active advocates, educators, and professionals in helping patients make informed decisions about their personalized treatment. The article “The Transformation of Breast Cancer Management,” published in the Journal of Oncology Navigation & Survivorship Special Issue in October 2016, will be a primer to the additional information presented in this article to promote learning and evidence-based practice so navigators can continue appropriate breast cancer patient education and follow-up as an active multidisciplinary team member.9

To Treat or Not to Treat Ductal Carcinoma in Situ

There is current interest in evaluating different treatment approaches to ductal carcinoma in situ (DCIS) of the breast because studies suggest that half the patients with this subtype of cancer may not progress to a potentially life-threatening disease.10,11 There is a view toward low-grade DCIS arguing that it should be regarded as a risk factor for a subsequent breast cancer rather than a malignant disease by itself. DCIS is a noninvasive breast lesion diagnosed in more than 60,000 patients annually in the United States, currently accounting for 20% to 25% of all breast cancer diagnoses.12 The standard treatment includes lumpectomy or mastectomy and adjuvant radiation if warranted, as well as endocrine therapy.13 A 2015 article in JAMA entitled “Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ” fueled the controversy and confusion by stating that removing DCIS lesions has not shown a reduction in the incidence of invasive breast cancers and suggested the standard treatment may be too aggressive.14 This observational study did not address the accuracy of the DCIS diagnoses, whether surgery truly had clear margins, the quality of follow-up care, such as regular mammograms, and if any patients received hormonal therapy to prevent recurrence.15

To address the possibility of no treatment for this early stage of breast cancer, 2 trials in Europe are comparing observation with standard surgical excision with or without adjuvant therapy for women with low-risk DCIS.16,17 The trials define as low-risk women ≥46 years of age without a family or personal history of breast cancer; who were diagnosed with screen-detected calcifications alone; are asymptomatic; and with the diagnostic needle core biopsy determined not to be high-grade. Patients are randomized to surgery versus observation alone consisting of an annual mammogram and exam. The primary endpoint is 10-year ipsilateral invasive breast cancer–free percentage. Current concerns are patient preference and comfort with observation only. Memorial Sloan Kettering Cancer Center examined their DCIS patient population and raised the issue that only 16% of their patients met the study criteria, and from the group that had surgical excision, 20% were upgraded to have invasive breast cancer on final pathology.18 Interestingly, the tumors were heterogeneous in regard to tumor grade, size, receptor status, and nodal involvement, and all did not fit a profile of low risk. Fortunately, DCIS outcomes are excellent for the majority of patients. Ongoing research will contribute to any evidence-based treatment decisions made by the patient and physician related to the patient’s personalized risk factors.

Surgery

The 2016 article entitled “The Transformation of Breast Cancer Management” discussed the national trend of an increase in the number of therapeutic mastectomies for breast cancer.9 A study shows that the impact of the 2014 publication of margin guidelines that endorsed a minimal negative margin has reversed this trend and led to an increase in the overall lumpectomy rate and a decrease in the mastectomy rate.19 In 2014, the American Society for Radiation Oncology and the Society of Surgical Oncology announced a new consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stage I and stage II invasive breast cancer that were endorsed by the American Society of Breast Surgeons and the American Society of Clinical Oncology (ASCO).20 The guideline defined negative margins as no ink on tumor to optimize ipsilateral breast tumor recurrence. Wider margin widths had been the previous guideline and often led to more surgery, such as a re-excision or mastectomy, with rates ranging from 23% to 38%.21 The abstract released at the 2017 ASCO Annual Meeting showed a 13% increase in the rate of lumpectomies and a decrease in unilateral mastectomies from 27% to 18%.19 The change in the guideline also addressed the trend for an increase in contralateral prophylactic mastectomy as a decrease in bilateral mastectomies went from 21% to 16%. The change in the guideline was made possible by a grant from Susan G. Komen that supported a meta-analysis of margin width and ipsilateral breast tumor recurrence from a systematic review of 33 research studies and evidence-based medicine published from 1965 to January 2013.20 Morrow summed it up best by stating “this rapid change, observed within 2 years of the guideline’s dissemination, illustrates the willingness of the surgical community to adopt evidence-based practices that improve outcomes for their patients.”22

For de novo stage IV breast cancer or patients presenting with stage IV disease initially, the decision to resection the primary tumor to improve outcomes remains controversial. Two studies assessed if resection of the primary tumor made a difference on overall survival. The Turkish Study (Protocol MF07-01) found an overall survival benefit of 42% at 5 years with surgery versus 25% with systemic therapy alone.23 Survival in the first 3 years was equal but separated with a median improvement of 9 months. The greatest benefit was seen in patients with estrogen receptor–positive (ER+), HER2– disease, those with solitary bone metastases, and women younger than 55 years. A worse prognosis was seen in patients with multiple liver and/or pulmonary metastases who underwent initial surgery.

In the United States study, surgery did not impact overall survival for de novo stage IV breast cancer irrespective of tumor subtype.24 All patients received first-line chemotherapy per the treating physician’s choice, and then the group was divided into responders and nonresponders. Responders to chemotherapy, whether they achieved a complete response or stable distant disease, were referred to discuss elective surgery. Over one-third of the responders elected to proceed with surgery, so now the comparison was directed at responders only to avoid bias in comparing survival between responders and nonresponders. The median survival with surgery was 71 months versus 65 months without surgery, and improved survival was not seen in any subgroup (ER+, HER2+). The data remain mixed to suggest any benefit from surgery, so this scenario becomes an individual discussion between the patient and physician.

Cryoablation, an alternative to surgery in the treatment of early-stage invasive breast cancer, is being studied. Cryoablation of small breast tumors in early-stage breast cancer in the FROST trial is being compared in 2 arms; one arm with low-risk patients aged ≥70 years treated with cryoablation followed by adjuvant therapies, and the second arm with moderate-risk patients aged 50 to 69 years receiving the same treatment as arm 1.25 The primary outcome determinant is successful tumor ablation defined as absence of residual, viable, invasive, or in situ carcinoma at 6-month post-cryoablation biopsy. Secondary outcome measures are local tumor recurrence, satisfactory breast cosmetic results, and adverse event assessment over 5 years. If successful, this could be another treatment option for breast cancer patients who are not comfortable undergoing surgery and preparation time.

Neoadjuvant Chemotherapy

Navigators understand that surgery is not always the first treatment for breast cancer, and the impact on survival from undetected micrometastases has yet to be determined with analysis of clinical trials.26 Patients with early-stage breast cancer are candidates for neoadjuvant therapy if breast-conserving surgery at diagnosis is not possible due to tumor size, or if the cosmetic outcome would be poor due to tumor location. Currently, navigators are aware to prepare patients with triple-negative breast cancer (TNBC) or HER2+ cancer for a possible neoadjuvant therapy discussion because these subtypes would receive chemotherapy in their treatment course and are associated with a high response rate.27 Patients with TNBC are normally offered standard anthra­cycline- and taxane-based chemotherapy regimens.13 The addition of carboplatin to anthracycline- and taxane-based neoadjuvant chemotherapy remains controversial, with some experts in favor of adding it weekly for patients with tumors >3 cm, clinically positive nodes, or stage III disease.27

Newer HER2-targeted agents in the NeoSphere and TRYPHAENA trials allow more effective inhibition of HER2 and expand options for HER2-targeted neoadjuvant therapy based on the patient’s risk factors and overall health.28,29 With the progression of newer agents over the past decade, this aggressive form of breast cancer has become a targeted and treatable disease. A study from Italy randomized patients with early HER2+ breast cancer to 9 weeks versus 1 year of trastuzumab, and after more than 5 years of follow-up the disease-free survival is 85.4% for the weekly therapy and 87.5% for the 1-year treatment.30 The shorter administration had less cardiac toxicity, but the standard remains for trastuzumab to be administered for a 1-year duration. These new data have led to discussions on treating elderly patients with a shorter course as well as the financial savings associated with decreasing the treatment.31 Also, cancer centers in Germany have been administering trastuzumab subcutaneously versus intravenously, and patients expressed a clear preference for the subcutaneous route, with the time savings cited as the greatest benefit.32 The centers had greater flexibility in scheduling patient appointments but did receive a lower reimbursement rate. This could be an answer for areas facing oncology staff shortage, and with less financial toxicity for patients.

Radiation

Navigators understand to support all their patients to the best of their ability, but some populations require more intense navigation, and this was a point in a study about the timing of radiation in DCIS patients. DCIS patients, identified through the Missouri Cancer Registry, received radiation therapy 8 or more weeks after initial surgery, which was considered a delay.33 After adjusting for demographics and tumor prognostics, the risk of ipsilateral breast tumors was 26% higher for women who had delayed radiation therapy. Subgroups that were noted to be affected more by delays in radiation therapy were African American women, single women, and those who received Medicaid. This is an example where a breast nurse navigator could be involved to improve timing of care using the metric Patient Transitions from Point of Entry from the AONN+ domain Research/Quality/ Performance Improvement with the transition modality surgery to radiation (Figure 4).

 

A 2015 study boosts the current trend of thinking that DCIS is not cancer and does not have to be treated as such. This observational study looked at women in the Surveillance, Epidemiology, and End Results Program from 1988 to 2011 who had received a diagnosis of DCIS and concluded that 20 years after the initial diagnosis, 3.3% had died of breast cancer, which was almost identical to the rate of women generally.14 Also, those who received radiation had the same risk of dying of breast cancer 10 years out as those who did not. The subtypes that did not have the equivalent rates were African American women and those <40 years of age and who were identified as needing radiation treatment.

Navigators are lifelong learners and need to stay informed about recent studies around controversial issues such as DCIS and be cognizant of exceptions in the data.

Chemotherapy

In the 2016 article “The Transformation of Breast Cancer Management,” clinically applicable tools and visual aids are discussed that use gene expression profiling to help quantify decisions on recurrence and survival risk for individual patients and treatment benefits with the addition of chemotherapy and endocrine therapy in early-stage breast cancer.9 Oncotype DX, Adjuvant! Online, and PREDICT are reviewed and explained. Following the 2016 publication of findings from the MINDACT randomized phase 3 clinical trial, the ASCO clinical practice guideline now recommends the use of the MammaPrint genomic test for women with early breast cancer.34 The MINDACT study demonstrated that 46% of breast cancer patients whose tumors were classified as low-risk via MammaPrint can avoid chemotherapy and still have good survival rates.35 The study showed that patients 5 years out from diagnosis who were identified as being at high risk for breast cancer recurrence based on clinical-pathologic factors were classified as low-risk based on MammaPrint and did not receive adjuvant chemotherapy, but they had similar rates of disease-free survival. Some of the high-risk features were lymph node–positive disease, grade II/III, tumor size >2 cm, and age <50 years.36

Endocrine Therapy

Data from the national Patient Navigation Research Program showed that navigated patients eligible for hormone therapy were more likely to start treatment than non-navigated eligible patients.37 Studies show that nonadherence remains a significant challenge for women receiving hormone replacement therapy because of worsening vasomotor, sexual, physical, or psychosocial symptoms.38,39 This presents a challenge for navigators working with women in this phase of care to be attentive to such symptoms and improve hormone therapy adherence with symptom interventions. Even exercise can ease some of the side effects, such as joint pain and weight gain, as shown in the Hormone and Physical Exercise study.40 Women who had been taking an aromatase inhibitor for at least 6 months were randomized to participate in a year-long exercise program or receive usual care; the exercise group had 20% to 30% less joint pain as well as a drop in body fat percentage and body mass index. This challenge can be monitored by the AONN+ metric on Treatment Compliance under the domain Coordination of Care/Care Transitions, in which the percentage of navigated patients who adhere to institutional treatment pathways per quarter are assessed (Figure 5).

Another study presented at the 2016 San Antonio Breast Cancer Symposium supported the trend of an aromatase inhibitor is administered for 10 years to offer more benefits than taking one for 5 years.41 There was no significant improvement in overall survival, but letrozole provided a significant improvement in a breast cancer-free interval, including recurrence, contralateral breast cancer as the first event, and distant recurrence. Because continuation of hormone therapy does have side effects, physicians are selective about extending therapy and may focus this addition on women with characteristics of high risk of recurrences such as node-positive or large, high-grade tumors.

Special Populations Men

According to the American Cancer Society, more than 2400 men will be diagnosed with invasive breast cancer, over 400 will die of the disease, and this rate has been stable over the past 30 years.42 The lifetime risk for a man to get breast cancer is 1:1000, which is 100 times less than acknowledged in women.42 An abstract at the 2017 ASCO Annual Meeting using the National Cancer Database looked at trends in clinical and pathologic features, treatment, and overall survival between male breast cancer patients from 2004 to 2009 and from 2010 to 2014.43 The conclusion was that male breast cancer patients are being treated similarly to female patients, but they are less likely to receive adjuvant hormonal therapy. There has been an improvement of overall survival, but there was no explanation of why 16% of patients with hormone-positive tumors did not receive therapy.

A clinical trial by the European Organisation for Research and Treatment of Cancer with men from Europe and the United States is collecting and analyzing medical information and tumor samples from male breast cancer patients to help doctors learn more about the disease.44 The study, which is no longer accruing patients, is using disease characteristics, patterns of treatment offered, and biologic characterization of the disease to investigate clinical outcomes such as survival, progression-free survival, time to locoregional relapse, time to distant relapse, and time to the second primary. The final collection date for primary outcome measure was June 2017, so results should be released in the near future to further increase knowledge on this breast cancer subgroup.

Currently, in the absence of high-quality data, the indications for breast cancer treatment for males mirror those for women, and the National Comprehensive Cancer Network (NCCN) guidelines for breast cancer care do not differentiate between the sexes.

Pregnant Women

The NCCN does have guidelines for a pregnant woman with a confirmed breast cancer diagnosis. The care is similar to a nonpregnant breast cancer patient except for13:

  • Chemotherapy is not administered during the first trimester of pregnancy. There are inadequate safety data to recommend taxanes during pregnancy; however, weekly paclitaxel after the first trimester is permissible if disease status clinically indicates the need. Anti-HER2 therapy is contraindicated
  • Radiation therapy should not be administered during any trimester
  • Blue dye used with the sentinel lymph node biopsy is contraindicated, but the radiolabeled sulfur colloid is safe to use

An abstract at the 2017 ASCO Annual Meeting summarized data from a multicenter retrospective study to address the question if pregnancy after breast cancer increases the recurrence rate.45 Pregnant patients after breast cancer were matched according to tumor differentials and treatment with patients who did not get pregnant, and after 10 years of follow-up, there was no difference in disease-free survival in estrogen-positive patients. Interestingly, the pregnant estrogen-negative patients had a 42% lower chance of dying, and this opens an avenue for more research to explain why pregnancy may be a protective factor in this group.

The International Breast Cancer Study Group has a trial underway that is evaluating the pregnancy outcomes and safety of interrupting endocrine therapy for young women with endocrine-responsive breast cancer who desire pregnancy.46 The participants will complete 18 to 30 months of endocrine therapy and then have a 2-year break for pregnancy and/or breastfeeding. The participant will then resume therapy for a total of 5 to 10 years. The study is continuing accrual that started in 2014 with the goal of 500 final participants. This study will possibly solidify recommendations from the 2017 ASCO presentation as well as answer the impact of breastfeeding.

Geriatric Patients

The research trend has been to not support radiation in older women (>70 years) with early-stage, estrogen-positive breast cancer, and no high-risk pathologic features, but what about other breast cancer treatments?47 Surgery appears to remain the same between the ages unless there are mitigating circumstances. Older women may be recommended chemotherapy, but the impact of potential side effects on a woman’s quality of life should be the center of attention when weighing the risks and benefits of any treatment plan. The NCCN has guidelines to support decisions in older adult oncology, with an emphasis on biologic as well as chronologic age consideration for breast cancer treatment decisions.48 The decision tree starts with the questions of the patient’s risk of dying of cancer in relation to their life expectancy and if they have decision-making capacity. Life expectancy calculators are built in for this discussion with the patient and family, and a route to palliative care guidelines is readily available.

Age is the main risk factor for breast cancer, and women are living longer and healthier than their peers in the past.49 A comprehensive geriatric assessment is crucial to help older patients make decisions about breast cancer care, and the NCCN recommends this evaluation in the senior population (>65 years of age) to assess life expectancy and morbidity risk.48 Often it is not routinely completed due to time constraints and employee resources for administration of the calculations.48 Instruments are available at the Cancer and Aging Research Group website that can be self-administered by patients to help in the decision-making process.50 The Geriatric Assessment Tool assesses functional status, comorbidities, medications, nutritional status, cognitive function, and psychosocial status, but it has not been used routinely in oncology care due to the time and resources needed for completion.51 Research continues on this tool for a future breast-specific predictive model.52 The more practical tool on the same site for clinical practice is the Chemo-Toxicity Calculator that looks at sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables.51 The results can be printed for the physician to use with the patient in treatment decision discussions. This is a resource navigator can share with the older patients if they struggle with treatment decisions.

Another instrument is the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) that stratifies the risk for chemotherapy toxicity.53 This 8-item assessment incorporates the chemotherapy regimen as well as patient variables and separates toxicity scores into hematologic and nonhematologic. It is completed by a healthcare professional who must calculate a Chemotox score and complete several mini assessments to obtain a CRASH score. An online interactive version can be found at https://moffitt.org/for-healthcare-providers/clinical-programs-and-services/senior-adult-oncology-program/senior-adult-oncology-program-tools/. The NCCN has recommended additional validation of this tool.

Each instrument to help predict treatment risk employs patient self-reporting. It is important to analyze such reports because patients may not report personal limitations to their fullest and not describe deficits precisely. The increasing geriatric population can be a challenge to the oncology realm in the future, and time-efficient comprehensive geriatric assessments are needed. The Chemo-Toxicity Calculator and CRASH scores are instruments that can assess for critical factors in the senior population.

Conclusion

Every treatment decision begins with the patient and involves their physical, mental, and spiritual health. Breast navigators ensure that patients have a voice and influential role in their care. Breast care remains a complex area with increasing options and new technology requiring less treatment time but with excellent survival results. It is an exciting era to see value-driven care measured by outcomes that are important to the breast cancer patient and supported by the multidisciplinary team with a patient-centered focus. Also, it is a historic time in the evolution of navigation as the personalized care is measured with evidence-based metrics in the care of breast patients and others.

References

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