Best Practices in Breast Cancer – October 2016 Vol 7
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Breast Cancer, Survivorship
The Transformation of Breast Cancer Management
Sharon S. Gentry, RN, MSN, AOCN, CBCN, ONN-CG
Breast Nurse Navigator
Novant Health Derrick L. Davis Cancer Center
If you are a female in the United States, your lifetime risk of being diagnosed with breast cancer is 1 in 8.1 If you are a male, the risk is 1 in 1000.2 This disease remains the most common cancer diagnosed among women, accounting for 1 in 3 cancers and appearing more often in women ≥50 years of age, with the average age at diagnosis of 61 years.3 In 2000, breast cancer incidence rates in women began decreasing, and a 7% drop from 2002 to 2003 was attributed to fewer women using hormone therapy after menopause because results from the Women’s Health Initiative study linked the use of hormone replacement therapy to an increased risk of breast cancer and heart disease.2 Breast Cancer Facts & Figures 2015-20162 shows trends for in situ and invasive breast cancer incidence rates remaining stable in the past decade, the result of widespread mammography screening that peaked in the early 2000s and now has stabilized.
When looking at race and ethnicity, breast cancer incidence rates are higher for white women than African American women except before the age of 40 years, and death rates are higher in each age group for African American women.4 According to the American Cancer Society,2 other racial and ethnic groups have lower incidence and death rates for the disease, with Asian Pacific/Islander women having the lowest rates. Over the past 30 years, the breast cancer death rate has dropped by 25%, but in women aged 20 to 59 years it remains the leading cause of cancer death.5 The more than 3.1 million breast cancer survivors in the United States are related to the declining breast cancer death rate seen since 1989 and has been influenced by earlier detection through screening and increased awareness, as well as improved treatment options.2
The world of breast cancer management is changing, just as the statistics for the disease has improved over the past decade. All navigators in the care continuum from outreach to survivorship need to stay abreast of the transformation as they support patients in the role of advocate, educator, team facilitator, and resource coordinator.
Breast Cancer Screening
Several topics in the screening arena for breast cancer have gained much attention over the past decade–breast density, digital mammography, magnetic resonance imaging (MRI), tomosynthesis, and screening guidelines. Navigators are in a unique role as patient advocates and educators for evidence-based changes to help the public understand the ongoing transformation of breast cancer screening.
High breast tissue density is a risk factor for breast cancer.2 Factors linked to breast density are younger, premenopausal or postmenopausal women who take hormone replacement therapy. Some women naturally have dense breast tissue throughout their lifetime due to family genetics.2 Dense breast tissue creates difficulty in the interpretation of images on mammograms.6 Breast density does not relate to breast size but is a comparison of denser breast tissue such as connective and glandular tissue in relation to the nondense tissue of fat.7 Fatty tissue areas show up dark on a mammogram, whereas dense connective and glandular tissue show up as white areas. Dense tissue and cancer both look white on film, so it is as if the radiologist is looking for a snowball in a snow storm when reading a mammogram of dense breast tissue.7
Since mammographic detection of breast cancer is challenging with women who have dense breasts, 28 states have laws that require the breast density level to be included in the final mammogram report and may also require that the women be informed if additional screening is warranted.8 A problem is lack of standardization in the education or how women are informed about their breast density, and with no set criterion of follow-up care such as ultrasound or tomosynthesis, insurance may not cover additional testing.9 The FDA is proposing an additional regulatory amendment to address breast density that would standardize nationwide notification in the letter women receive after their mammograms and give further direction on screening needs based on the density level.10 In July 2014, Representatives Steve Israel of New York and Rosa DeLauro of Connecticut introduced bill HR 5145 – Breast Density and Mammography Reporting Act of 2014 – in the House of Representatives to require breast density reporting to physicians and patients by facilities that perform mammograms. At the same time, Senators Dianne Feinstein of California and Kelly Ayotte of New Hampshire introduced a companion bill in the Senate.11 The bill was not enacted but has been reintroduced as HR 716 in February 2015 and was last referred to the Committee on Energy and Commerce, where no action has been taken on the proposal.12 Navigators interested in what their state is doing to address this concern can learn more at the Are You Dense advocacy website at http://areyoudenseadvocacy.org/.
The reasons why women with higher breast density are more likely to develop breast cancer have been unclear, but a recent United Kingdom–funded project found a key biological mechanism that may explain why dense breast tissue is a risk factor for breast cancer.13 Scientists from the University of Manchester generated molecular signatures from fibroblasts in dense breast tissue and found a cell communication network that could promote tumor formation. The c-Jun N-terminal protein kinase 1 (JNK1) pathway is a cellular communication network that modifies the activity of numerous proteins at the mitochondria or acts in the nucleus.14 The JNK1 network in the dense tissue instructed cells to release chemicals that caused inflammation and thus encouraged tumors to develop. Breasts with lower-density breast tissue did not express much JNK1 network activity. This research could drive new preventive trials in women with high-density breast tissue by designing drugs that interfere with the JNK1 network.13
The procedure for receiving a mammogram with film or digital mammography is the same, but the reading process has changed. For the past 35 years, film mammography has been used in breast cancer screening, as images are recorded on film, viewed by a radiologist using a light box, and physically stored in a jacket at the imaging facility.15 Studies have shown that breast cancers detected by breast self examination or physical examination were not always visible on film mammography.16,17 The advancement to digital mammography may address this concern. Digital mammography transmits images to a computer where radiologists can use software to manipulate underexposure or overexposure, and the views can be stored and sent electronically.15 Thus, the interpretation of images is improved with the exposure adjustment, and the possibility for providing remote consultations with other healthcare providers is enhanced. Digital mammography uses less radiation than film, is more sensitive in screening women younger than 50 years or those who are of premenopausal or perimenopausal age, and is more discerning for women with dense breast tissue of any age.18 de Gelder and colleagues showed that the number of ductal carcinoma in situ (stage 0, noninvasive) breast cancers detected was increased by 80% with the use of digital mammography.19
Magnetic Resonance Imaging
A breast MRI uses magnetic fields rather than radiation to create a detailed image of the breast by providing discriminating soft tissue contrast images, and it is not affected by breast density.20 Breast MRI is not a substitute for mammography and is not for women with low lifetime breast cancer risk factors because it can lead to a high rate of false-positive results. It is expensive, with an average cost of over $1200; that is 10 times as much as 1 mammogram.21 In 2007, an American Cancer Society–led expert panel published recommendations to use MRI as a supplement to mammograms for women with a high lifetime risk for breast cancer.22 This high lifetime risk group includes women with known genetic mutations linked to a higher breast cancer risk such as BRCA1, BRCA2, Li-Fraumeni or Cowden syndromes, a first-degree relative who had a genetic mutation but has not had personal testing, individuals with a lifetime risk of breast cancer ≥20%, or people who had radiation therapy to the chest between the ages of 10 and 30 years.
Digital tomosynthesis in breast screening uses x-rays to create a 3-dimensional (3-D) picture of the breast. This technique is trying to overcome 3 issues in mammography–the uncomfortable compression of the breast that’s required during a mammogram, compression that causes overlapping of the breast tissue, and avoiding a “flat” picture–by taking multiple images from many angles.23 In 2011, tomosynthesis was approved by the FDA to be used in combination with standard digital mammography for breast cancer screening.24 One goal is to help “see” better in women with dense breast tissue, because a better first look will decrease callbacks for additional imaging.23 Tomosynthesis is not in widespread use because it exposes patients to additional radiation dose, the exam may not be covered by insurance, and the benefits have not been fully substantiated by clinical trials.25 This pattern of use may be changing due to recent policy changes from the National Comprehensive Cancer Network (NCCN) and Cigna insurance. In August 2016, Cigna announced it would cover 3-D mammography for routine breast cancer screening, whereas in the past the company only covered 3-D mammography for diagnostic purposes and not for routine screening.26 This coverage change for Cigna was prompted by the July 2016 release of the NCCN Breast Cancer Screening and Diagnostic guidelines that recognize the value of 3-D imaging to improve cancer detection and decrease callback rates.27 It will be interesting to see if other major insurance companies follow suit.
Two recent European single-site tomosynthesis studies to substantiate the use of tomosynthesis as an efficient screening method showed an increase in cancer detection.28,29 One had a reduction in false-positive rates, and the other had a reduction in recall numbers. Friedewald and colleagues30 used geographically diverse sites and academic and nonacademic settings to repeat the findings of an increase in cancer detection rates and a decrease in recall rates. Women may be asked as they go for their annual mammogram if they would like a 3-D or tomosynthesis screening, but they may be asked to pay extra for the screening.
Nurses and navigators need to be aware of discriminatory issues in breast cancer screening as the more affluent clients may opt for dense tissue follow-up or tomosynthesis screening, and these options may not be available for the underinsured or uninsured until legislation is passed to ensure coverage. Also, they need to be able to address the confusion that is caused by conflicting guidelines from leading medical groups and educate women on what is the best personalized mammography screening schedule for them (Table 1). Do they initiate screening at 40 years of age, and is it every year or every other year? What is best for personalized care?
In 2009, the US Preventive Services Task Force (USPSTF) issued mammography recommendations that went against long-established guidelines for annual mammograms to start at age 40 years for all women.31 The USPSTF does not recommend annual mammograms at the age of 40 years and instead says the decision to initiate regular, biennial screening mammography before the age of 50 years should take into account the patient’s values regarding specific benefits and harms of the screening. For women aged 50 to 74 years, USPSTF recommends biennial screening mammography, and no mammography screening for women 75 years or older.31 In 2015, the American Cancer Society changed its recommendations and promoted mammograms every year starting at age 45 to 54 years, changing to every 2 years at the age of 55 years, and continuing for as long as a woman is healthy with a life expectancy of 10 years or longer. They advised women aged 40 to 44 years to start annual mammography if they desired.2 Again, another message that contradicts the decades-old public message for women to start mammography at the age of 40 years because it is the best tool available to screen for breast cancer, and it has helped reduce the breast cancer death rate in the United States.32 Major health organizations, including the American Society of Breast Disease, the American College of Obstetricians and Gynecologists, the American College of Radiology, and the Society of Breast Imaging, continue to recommend annual mammograms beginning at age 40 years. The recommendation controversy has created discussions around the benefits of mammography screening as well as the harm it can cause, such as false-positive findings that require additional imaging and commitment of follow-up time.
In one survey, 40% of women who experienced a false-positive mammogram result defined it as “very scary.”33 The experience was temporary, and despite undergoing a false-positive workup, most said they were glad they had undergone the test. In an earlier study by Schwartz and colleagues,34 more than 30% reported they would tolerate false-positive mammograms if it would avoid a breast cancer death. Overdiagnosed cancers are those detected by mammography that would never cause symptoms or result in death. Because there is no method to determine which cancers will cause no harm, all are treated with surgery, chemotherapy, radiation, or a combination of these treatments. The treatments can cause long-term psychosocial or physical effects for survivors.35 Each woman will individually interpret the benefits and harms of screening, and this should be done in a discussion with her healthcare provider. Interestingly, since the 2009 USPSTF recommendations caused a public controversy over screening, there has not been any measurable effect on women actually getting screened. A study by Pace et al looking at the trends of screening rates supported that screening has not gone down in any age group, including women in the 40- to 49-year bracket.36 Also, under the Patient Protection and Affordable Care Act,37 Medicare and most private insurance plans are now required to cover annual mammograms for women older than 40 years. The trend is that 1 standard will no longer fit all women, and guidelines based on individual risk, breast density, and family history will drive conversations between the woman and the healthcare professional on mammography initiation, frequency, and cessation.
Initiating Breast Cancer Care
Nursing navigation can be invaluable to a patient when they hear those words “you have breast cancer.” Breast cancer is not 1 disease. There are in situ or invasive types, and each type is further subtyped based on the tissue of origin. The prognostic factors such as size, histologic grade or type, proliferative rate, and stage of disease influence treatment. Also, molecular profiling contributes to the heterogeneity of the disease as hormone receptor and HER2 status are obtained on the initial pathology to help plan treatment. 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.38 Nurse navigators can improve communication among the healthcare team, expedite care, and ensure that the patient receives appropriate interventions throughout the care continuum.39 Upon diagnosis, many informed decisions need to be made, such as genetic assessment, surgical choice, possible neoadjuvant chemotherapy, and the 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. A nurse navigator has been shown to increase downstream revenue to the healthcare system by retaining patients in the system at this point in the care continuum.40
A discussion on family history is an important part of breast cancer screening since approximately 10% of all breast cancer is related to a hereditary disposition.2 As Angelina Jolie Pitt disclosed her personal experience 2 years ago, this has increased public awareness of family history with breast cancer.41 The most common breast cancer mutations are BRCA1 or BRCA2, but there are other genetic syndromes associated with a family history of breast cancer.42 Over time, women who carry a BRCA1 or BRCA2 mutation are more likely to develop a second cancer in both the ipsilateral and the contralateral breast as well as ovarian cancer.43 This is why testing is important in high-risk individuals preoperatively, because women who develop breast cancer in 1 breast and test positive for a mutation may have the information to decide for a bilateral mastectomy, or they may opt for breast-conserving surgery (BCS) and increased screening. Since the BRCA1 and BRCA2 mutations put the patient at risk for ovarian cancer, this factor becomes a vital part of the survivorship care plan for future screening or preventive surgery.43 Navigators need to be aware that genetic testing for genes associated with breast cancer is commercially available and is easy to order, but because of the clinical information that needs to be addressed, psychosocial concerns for the patient and family, and the development of a plan to address the implications of the results, a qualified healthcare professional trained in genetics should provide pretest and posttest counseling.44
Just having breast cancer in the family does not mean one will be at high risk for developing the disease since breast cancer is a common malignancy in women, and the 2 or more relatives with the disease may be older at diagnosis.45 A survey showed that women undergoing a mammogram could not give a correct estimate for their personal risk to develop breast cancer based on family history.46 Forty-four percent underestimated their risk, 45% overestimated it, 9% correctly stated their risk, and 40% stated they never had a discussion of the probability with a healthcare provider.46 All navigators need to be aware of individuals with a family history that can be associated with an increased risk of a mutation for breast cancer (Table 2) and offer a referral to a healthcare professional trained in genetics.44
Overall, people are protected from genetic discrimination if they have a gene mutation that increases their risk of cancer, and patients may be concerned over who has access to see the genetic results. The Genetic Information Nondiscrimination Act (GINA) became federal law in 2008 and prevents discrimination based on genetic information in determination of health insurance eligibility, health insurance rates, or relevance for employment.47 Also, the National Cancer Institute (NCI) affirms that the Privacy Rule of the Health Information Portability and Accountability Act protects genetic results because a person’s genetic information is considered health information.47 There are exceptions to this law, and patients need to be aware that the federal law does not protect them from personal life insurance, disability insurance, or long-term care insurance inquiries about their genetic history. GINA does not cover members of the military.48 Navigators need to be able to inform patients about genetic discrimination protection so high-risk individuals will not be deterred from testing that could influence their health maintenance.
Breast Cancer Treatment
Once 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 biologic discrete diseases that ranges from in situ (noninvasive, stage 0) to invasive (stages I-IV) with tissue subtypes of ductal, lobular, lymphoma, sarcomas, and others.49 Navigators need to be aware of advances in surgery, radiation therapy, chemotherapy, and hormone therapy to be active advocates, educators, and professionals helping patients make informed decisions about their personalized treatment.
Breast surgery has evolved from the radical mastectomy promoted by Halsted in the 1950s and 1960s to the modified radical, simple, or skin-sparing mastectomy choices of today.50 Mastectomy is removal of the whole breast and is indicated with multicentric disease that involves more than 1 area of the breast, diffuse microcalcifications, tumor size that would not allow for an acceptable cosmetic outcome with BCS, or recurrence in a previously irradiated breast.51 A woman undergoing a mastectomy should be directed to discuss breast reconstruction with a plastic surgeon.47 BCS is also called lumpectomy, tylectomy, segmental mastectomy, partial mastectomy, or quadrantectomy, and the goal for BCS is to remove the tumor with a margin of healthy tissue and achieve an attractive result. BCS is indicated when tumor size, location, and characteristics allow the remaining skin to be spared.51 Radiation therapy may follow BCS to achieve survival rates that are equal to removing the breast.52 Patients with collagen vascular disease such as systemic lupus erythematosus or scleroderma may not be able to tolerate radiation due to skin reactions, thus BCS may not be the best treatment choice.53
Despite randomized controlled trials having found that survival is equal between women who undergo lumpectomy with radiation and those who elect to have their affected breast removed, a national trend shows a substantial increase in the number of therapeutic mastectomies for breast cancer.54,55 This trend has created much discussion in the lay press and editorials in the oncology literature on the factors influencing women to choose mastectomy. Cited predictors of influence are age <40 years, large tumor size, and lymphovascular invasion.56 Other factors are lobular histology, breast density, concurrent or prior contralateral breast cancer, family history, and use of MRI.57 Recent studies on early-stage invasive ductal carcinoma have shown that patients who underwent BCS had a higher survival rate–as much as a 13% lower breast cancer mortality in women older than 50 years with hormone-positive tumors compared with those treated with mastectomy alone or mastectomy with radiation.55,58
Along with the concern about rising mastectomy rates of the affected breast is the increase in contralateral prophylactic mastectomy (CPM). A review of the Surveillance, Epidemiology, and End Results data in the United States confirmed the contralateral prophylactic mastectomy rate has increased over the years for all cancer stages from 4.2% in 1998 to 11.0% in 2003.59 Kurian and colleagues60 did a similar review in California and found an increase in the rate from 2.0% in 1998 to 12.3% in 2011. Tuttle et al59 and Kurian et al60 cite factors associated with this choice as young patient age, lobular histology, white race, and higher education. Possible explanations for this trend include the increased awareness and use of genetic testing, improvements in reconstructive surgery techniques, and generational differences.61 A concern with the mastectomy choice with reconstruction over the BCS is the increased length of surgery, prolonged hospital stay, extended recovery time, and complications that may delay adjuvant therapy. Surgically removing a breast to prevent breast cancer may reduce the incidence of breast cancer in high-risk women (strong family history, atypical ductal hyperplasia or atypical lobular hyperplasia biopsy history, genetically positive test), but increased survival rates have not been established with CPM in women without these risk factors.62 A recent decision model study found that the maximum life expectancy gain for women who underwent CPM was 6 months.63 The authors included factors such as age, estrogen receptor status, and cancer stage groups. The results can be used to promote the concept that a CPM will not improve a woman’s survival if she does not have the hereditary breast cancer risk.63
Another topic in breast surgery has been the role of sentinel lymph node biopsy, and this has challenged the traditional thinking about complete axillary lymph node dissection (ALND) that has been the standard of care for decades.64 A recent review of 1070 publications on axillary interventions in breast cancer concluded that a complete ALND in BCS is associated with more harm than benefit.65 Harm equated to no survival benefit and a 14% risk of lymphedema with ALND, whereas the risk of lymphedema was 5% to 7% in sentinel biopsies. Caretta-Weyer and colleagues reported that women who met the criteria for avoiding ALND were those who did not have palpable, suspicious nodes, had tumors 3.0 cm or smaller, and had 3 or fewer positive nodes on sentinel biopsy.66 Again, a key consideration for this transformation in care was harm versus benefit.
Navigators need to understand that surgery is not always the first treatment for breast cancer. A landmark clinical trial on neoadjuvant chemotherapy, therapy given before surgery, has shown that more preoperatively treated women underwent lumpectomy and radiation therapy versus mastectomy, and rates of ipsilateral breast tumor recurrence after lumpectomy were similar in the 2 groups.67 Outcomes were best in women who showed a complete response or showed no evidence of disease at surgical staging. The trial showed that neoadjuvant chemotherapy could be used to study breast cancer biology or tumor response, but the effect of chemotherapy on micrometastases could only be hypothesized.67 This does not mean the cancer has been cured because the impact on survival from undetected micrometastases has yet to be determined in future analyses of clinical trials.68 At this time, chemotherapy before surgery has not demonstrated better survival, but is used for the inflammatory breast cancer subtype. It may convert an unresectable (too large) breast tumor to a resectable size and shrink large operable tumors to allow BCS such as a lumpectomy, as well as allow clinical and pathologic response to therapy to be observed.69 A strong disease-free survival advantage has been observed in women with estrogen-negative, progesterone-negative, and HER2-negative subtype breast cancer who have a complete pathologic response.70 The NCCN guidelines for breast cancer69 supports neoadjuvant chemotherapy for HER2 receptor–positive patients with a tumor ≥2 cm or patients who present with a positive node since there was a 57% to 66% complete pathologic response rate in this subgroup. There is a concern for patients with incomplete responses after neoadjuvant therapy in whom the recurrence rate is higher due to remaining disease, and there are ongoing research efforts through the NCI with additional chemotherapy after surgery for this population.71
The discussion on surgical trends and presurgical care treatment information reinforces the need for women facing breast cancer to have a multidisciplinary breast team that will share accurate and easily understood educational information based on the individualized cancer presentation. Navigators have been used to assist women through the maze of multidisciplinary breast care, especially among nonaffiliated practices and physicians.72 The involvement of nurse navigators can increase clinical trial participation. In a California community setting, Holmes and colleagues73 increased African-American patient participation in clinical trials from 3% to 7% over 2 years after a nurse navigator program was placed as a liaison between the academic center with clinical trial access and community physicians. Nurse navigators got to know patients on a personal level and deciphered how patients selected care based on their life circumstances. The NCI Community Cancer Center Program developed a minority matrix project to address barriers for minority clinical trial accrual.74 The matrix showed that navigators could improve clinical trial accrual with education about trials, advocate for trials in treatment decisions, and be a liaison between the research team and the patient. Rapid City Regional Hospital in South Dakota used navigation to assist the American Indian/Native American, Hispanic/Latino, African American, and urban/rural poor access to clinical trials, and 46% participated in a prevention or treatment clinical trial with their support.75
It is important for navigators to be aware of the changes in radiation treatment (RT) so they can be advocates for patients to explore options of care that can decrease treatment time, travel logistics, and expenses related to daily treatments. Some women chose a mastectomy due to the above barriers radiation can present, as well as loss of work time or inability to care for a family during the course of an RT.76 The choice may be different with information on more applicable radiation choices.
Advances have occurred in RT over the past decade, such as radiation therapy following BCS now being widely accepted. Evidence shows that adjuvant radiation after BCS is standard to eradicate microscopic disease that may be present near the original tumor site 30% to 40% of the time.77 The role of postmastectomy radiation and its impact on overall survival have more recently been demonstrated.78 Many patients erroneously believe that if a mastectomy is chosen, RT will not be necessary after surgery because the breast tissue is removed. Navigators assisting breast cancer patients with treatment decisions or explanations need to be aware that according to the NCCN guidelines listed below, standard radiation is indicated after a mastectomy for a select population of patients69:
- Women with 4 or more positive axillary lymph nodes
- Women with 1-3 positive axillary lymph nodes and a tumor >5 cm
- Clinically or pathologically positive ipsilateral internal mammary lymph nodes
- Tumors 5 cm
- Patients with less than 1-mm margin or positive margins
- Neoadjuvant chemotherapy patients based on prechemotherapy tumor characteristics
When navigators speak with their patients, they may hear that the delivery of radiation is no longer just the standard 6.5 weeks (33 days) of whole breast irradiation. There is an increase in the use of a hypofractionated course of whole breast irradiation over 3 to 4 weeks, accelerated partial breast irradiation after BCS over 1 week, and intraoperative dosing.79 Also, the patients may describe use of a deep inspiration breath hold technique to prevent radiation-induced heart disease.80
Giving radiation in larger doses over a shorter period of time is known as hypofractionated radiation therapy or accelerated breast irradiation.79 Whelan et al81 demonstrated after 12 years of follow-up on hypofractionated radiation therapy that the results were not inferior to the longer standard treatment for BCS participants who had invasive breast carcinoma, negative axillary nodes, no disease at the margins, no tumors greater than 5 cm, or were treated with axillary dissection. It has been shown that patients do not select breast irradiation because of the inconvenience of the therapy, such as transportation, lengthy travel time, missed time from work, cost, or other daily commitments. Women who desire BCS may find the shorter course more appealing to their time commitments and less costly than standard treatment.
Accelerated partial breast irradiation is an attractive alternative for patients who live far from radiation facilities and is an even shorter treatment than hypofractionated radiation. It can be completed in 1 week and is typically delivered over a 5-day period with twice-a-day appointments spaced 6 hours apart.76 It targets the breast tissue around the lumpectomy site since this is the area at highest risk for recurrence, spares healthy tissue from unnecessary radiation, and can be delivered many ways, including 3-D conformal external beam radiation, bead or seed implants, or a balloon catheter device placed into the lumpectomy cavity.82 The 2009 American Society for Radiation Oncology consensus guidelines cite the criteria for appropriate patients to use this technique as women with early-stage (I or II) breast cancer who have small tumors (3 cm), negatice margins, and negative sentinel lymph nodes 83 ( Initial research involving single-institution and registry series with the MammoSite (type of accelerated breast radiation treatment device) has shown no statistically significant difference in ipsilateral breast tumor recurrence rates compared with standard therapy of 6 weeks, although follow-up time is short.84 Hattangadi et al caution that it may be several years before there is definitive evidence that this technique is equivalent to whole breast radiation in areas of disease control, toxicity, and cosmetic results.85
To deliver radiation therapy in even fewer treatment sessions, clinical trials are ongoing with a single dose of intraoperative RT as another form of accelerated partial breast irradiation. The TARGIT-A trial was designed for patients with breast cancer suitable for BCS but who had limited access to radiation therapy or those who had access but were influenced by the prolonged course of whole breast radiation to choose mastectomy.86 Five-year results from a multiple-country trial show that intraoperative radiotherapy is an alternative approach in a carefully selected population that is at low risk for local recurrence. The 5-year local breast recurrence and mortality rates from breast cancer were similar to external beam radiation that was delivered over weeks.
In recent years, there has been much discussion about radiation increasing the risk of heart disease and leading to heart attacks, surgeries such as a bypass or angioplasty, or even heart-related death.87 Schubert and colleagues88 looked at methods currently used to avoid cardiac irradiation, especially when treating the left breast, that implement the use of 3-D computed tomography with planning software to improve prescribing the radiation dose to the targeted area and avoiding unnecessary treatment of tissue. In cases where a small portion of the heart cannot be avoided due to the location of the surgical bed, a deep inspiration breath hold technique can be used with the patient.80 Hayden and colleagues explain that the patient is verbally coached to hold their breath, usually 15 seconds in duration, during RT planning and after a deep inspiration.80 Special equipment monitors the breathing pattern that will allow RT to be given when the patient is holding a deep inspiration. When the chest is expanded with a deep inspiration, the breast is pushed away from the heart and thus minimizes the RT dose to the heart tissue. Future heart risks should not be the reason to avoid RT if it is a needed component of treatment, because there are ways to minimize the exposure to the heart.
To further personalize care with radiation therapy, there continues to be research supporting no radiation in older women (>70 years) with early-stage, estrogen-positive breast cancer with no high-risk pathologic features.89 Older women who could take tamoxifen after a lumpectomy had no significant benefit in survival, time to distant metastasis, or ultimate breast preservation with the addition of RT.90 The trial goal was to offer a select cohort of women an option that might decrease morbidity, allow for continuation of social activities, and not confound other medical issues. The trial confirmed that the option of BCS without radiation therapy can be a discussion point between the patient and the radiation oncologist.90 Albert et al also supported no RT for women aged 75 to 79 years with low-grade tumors who had at least 1 pathologically sampled lymph node and could benefit from hormone therapy.91
Systemic therapy with endocrine therapy or chemotherapy helps cure and control the progression of early-stage breast cancer, but there are also side effects, quality-of-life concerns, long-term effects, and cost issues with therapy.92 Chemotherapy treatment decisions are guided by gene expression, tumor staging (size, growth rate, nodal status, and metastasis), and patient-specific characteristics such as age, menopausal status, comorbidities, and overall health.93 The one-size-fits-all philosophy of chemotherapy for invasive breast cancer is inappropriate. Personalizing medicine to the tumor genomics and to the patient characteristics allows the benefits of systemic therapy to outweigh the risks to the patient. HER2 status is an example of gene expression–guided therapy–the current treatment for HER2 positivity includes chemotherapy along with an anti-HER2 monoclonal antibody. HER2 is a type of tyrosine kinase receptor that is overexpressed in 20% to 25% of breast cancer cases.94 This positivity or overexpression indicates a more aggressive state with angiogenesis promotion and a higher growth rate.95 But trastuzumab (Herceptin), an anti-HER2 monoclonal antibody, specifically targets the extracellular area on these cells and causes receptor inhibition that disrupts the signaling for growth.95 The current treatment for HER2 positivity includes a choice of chemotherapy along with the drug Herceptin given every 3 weeks for a year, and currently there is an improved 10-year survival from 75% with chemotherapy alone to 84% with the addition of trastuzumab.96 Oral chemotherapy agents are becoming more prevalent in breast cancer treatment, and navigators need to be aware of compliance issues with this modality.97
Clinically applicable tools and visual aids that use gene expression profiling are being used to help quantify decisions on treatment in early-stage breast cancer. The aids are predictive models to help estimate the recurrence and survival risk for individual patients and treatment benefits for the additional chemotherapy as well as endocrine therapy.
For women with hormone receptor–positive breast disease, Oncotype DX is a genetic assay profiling tool that uses a sample of breast cancer tissue to analyze the activity of 21 genes to quantify the risk of recurrence and predict responsiveness to hormone therapy and chemotherapy.98 This subgroup of favorable breast pathology has been an area of uncertainty for patients and their doctors because the likelihood of distant recurrence with surgery and tamoxifen is 15% at 10 years versus a 3% to 10% survival benefit with chemotherapy.99 The NCCN breast guidelines suggest Oncotype DX as an option for women with 0.6- to 1.0-cm tumors with unfavorable features (high growth rate), node-negative or with 1 to 3 positive lymph nodes, HER2 negative, and hormone receptor positive.69 The recurrence score, as well as personal patient features such as overall health, is used in estimating the benefit of chemotherapy. Patients receive a numeric score that is shown on a graph, and those with a high score benefit from chemotherapy, whereas patients with a low score, even with positive lymph nodes, do not receive a benefit from additional chemotherapy.98 The intermediate score group makes an informed decision to take or omit additional chemotherapy based on a conversation with their medical oncologist. The TAILORx trial100 was launched in 2006 to randomize women who fall in the intermediate range to either hormone therapy alone or hormone therapy with combination chemotherapy. Hopefully this clinical trial will clarify the score or point at which patients’ hormonal therapy alone is sufficient treatment and which patients will not receive benefit from chemotherapy.
Adjuvant! Online is a computerized algorithm decision-making tool for healthcare professionals that estimates the risk of breast cancer–related mortality or relapse without systemic adjuvant therapy.101 The estimate is based on patient age, tumor size, nodal involvement, histologic grade, overall health, lymph node involvement, and hormone receptor status, and it does not apply to HER2-positive patients.102 The overall health feature allows the comorbidities of the patient to be adjusted from normal health to major health concerns, and this allows a risk estimate based on the patient being able to tolerate treatment. The estimate shows the benefits expected from adjuvant chemotherapy or endocrine therapy. Printed sheets are provided in simple graphic formats that the healthcare professional can use in consultation with a patient.102 For example, the patient will be explained that the risk of relapse is “x” over the next 10 years, and this can be reduced to “x” with endocrine therapy, and an additional “x” will be gained by using chemotherapy.
PREDICT is the first and only model to include HER2 status and the mode of detection.103 The PREDICT online program forecasts 5- and 10-year survival estimates using the histopathology of the breast cancer.104 Wishart and colleagues105 included mode of detection such as screen-detected, symptomatic, or unknown because there is growing evidence that there is a survival benefit of reduced systemic recurrence for asymptomatic detection when compared with symptomatic cancers of the same stage. It is a general guide to possible outcomes in individual pathologic cases and does not use overall health of the patient in the estimate. Graphics are provided for the visual learner (www.predict.nhs.uk/predict_v1.2.html) with statements that reflect:
- XX out of 100 women are alive at 5 years with no adjuvant therapy after surgery
- An extra X out of 100 women treated are alive because of hormone therapy
- An extra X out of 100 women treated are alive because of chemotherapy
- An extra X out of 100 women treated are alive because of hormone therapy and chemotherapy
- An extra X out of 100 women treated are alive because of hormone therapy, chemotherapy, and trastuzumab
Katz and Morrow describe the turmoil breast cancer patients can experience in making decisions about treatment.106 They describe patients focusing on the overall threat of cancer coming back versus the benefits or harms of the treatment options. Patients equate recurrence with death, and this can influence the decision for treatment. Duric and colleagues107 describe anticipated regret as a patient selecting the most aggressive therapy so if a recurrence is experienced, the patient would feel better knowing everything possible was done to avoid it, and this gut response about their immediate feelings on treatment may drive the decision to overtreat breast cancer. Anticipated regret has been justified as to why women with breast cancer take chemotherapy when the overall 10-year disease-free benefit is less than 2%.108 Clarifying treatment outcomes is a challenge for clinicians since patients process information on an individual, personal basis. Evidence-based care such as the NCCN guidelines, evaluative visual aid tools like PREDICT, Oncotype DX, and Adjuvant! Online, as well as ongoing clinical trials can promote understanding of personalized outcomes for breast cancer patients.
Endocrine treatment decisions are based on the estrogen receptor status of the breast cancer tissue. A breast cancer patient is either estrogen receptor–positive (ER+) or estrogen receptor–negative (ER–). ER+ patients will have a treatment discussion on endocrine or hormone therapy choices.
Endocrine therapy is used to block estrogen-dependent tumor growth (ER+), and it has grown from the gold standard of tamoxifen for all hormone-positive breast cancer patients to aromatase inhibitors (AIs) that include anastrozole, exemestane, and letrozole.69 Tamoxifen is a selective estrogen receptor modulator (SERM) that blocks the effects of estrogen in the breast tissue by sitting in the estrogen receptors and completely binding to the receptor site.109 It is the therapy of choice for premenopausal women needing endocrine therapy.110 Because tamoxifen acts like an estrogen in some tissue, it has less than a 2% risk of promoting uterine cancer but can increase the risk of major blood clots.111 So someone with a clotting history may not be prescribed tamoxifen. Other SERMs are raloxifene, which reduces the risk of invasive breast cancer in postmenopausal women who have a higher than average risk for the disease, and toremifene, which is designed for postmenopausal women diagnosed with metastatic hormone-positive breast cancer.112
AIs work by stopping estrogen production by preventing the production of estradiol, a type of estrogen.113 Since aromatase promotes estrogen production outside the ovaries, AIs are appropriate for postmenopausal women or premenopausal women without ovarian function.114 Women who take AIs can have side effects such as bone and joint symptoms, osteoporosis, and genitourinary symptoms.115 A woman at high risk for fractures or severe osteoporosis may be directed to another endocrine therapy. There is a role for endocrine therapy to be used neoadjuvantly in postmenopausal women to shrink tumors or control disease if comorbidities limit the use of other therapies such as surgery or chemotherapy.116
SERMs or AIs are normally taken orally for 5 years. Recent clinical trials have challenged this 5-year rule.117,118 In the MA.17 trial, Goss and colleagues116 randomized postmenopausal women to a placebo or letrozole after 5 years of tamoxifen; they showed the risk of metastatic disease was reduced by 61% for those on the letrozole arm, but more fractures were seen in this group. The trial continued as MA.17R with a focus on the effects of treatment with an AI for 10 years rather than just 5 years after any duration of prior treatment with tamoxifen. It showed that treatment with an AI for an additional 5 years after initial treatment with an AI was valuable in preventing disease recurrence.119 The ATLAS study randomized young premenopausal women who had been taking tamoxifen for 5 years to continue for another 5 years or to stop immediately.118 Results showed that women who had continued tamoxifen treatment beyond 5 years had a 25% lower recurrence rate and a 29% lower breast cancer mortality rate.118 These trials transformed the current use of hormone therapy for long-term reduction in risk, and it will be interesting to see if further endocrine therapy extension will provide better outcomes.
Promoting Evidence-Based Practice
As screening, diagnosis, and treatment for breast cancer evolve over time, new procedures and protocols will include consideration on the rising cost of care and the use of healthcare resources. A common theme in the past decade in breast care has been awareness of overdiagnosis and overtreatment.120 In the spirit of being good stewards to control the costs of healthcare and to recognize serious financial burdens to patients and families, the American Society of Clinical Oncology (ASCO) in 2012 contributed a list of 5 common practices in oncology care to the Choosing Wisely campaign that physicians would be discussing with patients about avoiding care that is unnecessary or in which harm may outweigh benefits.121 In 2013, 5 more practices were identified and incorporated into the ASCO Quality Oncology Practice Initiative to monitor their use and evaluate practice change.122 These practices do not replace individualized decision-making but promote discussions about procedures that show no evidence of supporting clinical value in oncology care. Navigators need to be aware of the ASCO recommendations to support evidence-based practices that physician-led teams may be discussing and implementing in breast patient care interactions. Navigators may get questions on why a physician is no longer ordering scans for follow-up or why her care is changing to a single chemotherapy drug versus using multiple drugs. Following are some examples with explanations from the 2012 and 2013 Choosing Wisely campaign that may be observed in current or future breast cancer care or in the community that nurses network.
- “Do not use cancer-directed therapy for patients with solid tumors who have the following characteristics: low performance status (3 or 4), no benefit from prior evidence-based interventions, not eligible for a clinical trial, and with no strong evidence supporting the clinical value of further anticancer treatment.”
These patients are limited to the bed or chair more than 50% of their waking hours and may experience worsened toxicity from treatment. Exceptions to this guideline include patients with functional limitations caused by another condition or those with disease characteristics such as HER2 positivity in a newly diagnosed patient who may have a high likelihood of responding to therapy. ASCO supports palliative and supportive care for this subset of patients.
- “Do not perform PET, CT, and radionuclide bone scans in the staging of early breast cancer at low risk for metastasis.”
There is a lack of evidence showing a benefit in asymptomatic individuals with newly diagnosed disease. The harms from such a practice include unnecessary invasive procedures, overtreatment, unnecessary radiation exposure, and misdiagnosis.
- “Do not perform surveillance testing (biomarkers) or imaging (PET, CT, and radionuclide bone scans) for asymptomatic patients who have been treated for breast cancer with curative intent.”
With earlier diagnosis of node-negative disease found with mammography and the efficacy of chemotherapy, radiation, and endocrine therapy, the risk for recurrence is low, and most women live out a normal life expectancy. There is no evidence to support the use of biomarkers or imaging in this population. ASCO supports using mammography with clinical breast examination as surveillance in this subset, with attention to patient history and physical examination on follow-up clinical visits. Most breast cancer recurrence is detected through clinical symptoms such as persistent pain, new lumps, or increasing shortness of breath, so diagnostic evaluation of new symptoms will be completed.
- “Do not use combination chemotherapy (multiple drugs) instead of chemotherapy with 1 drug when treating an individual for metastatic breast cancer unless the patient needs a rapid response to relieve tumor-related symptoms.”
Neoadjuvant and adjuvant chemotherapy for initial breast cancer treatment involves the use of multiple drugs, so at the time of metastasis, patients may be expecting the same again. The control base of thinking would be to attack the disease again with everything possible...“the more, the better” mindset. You don’t want patients to think fewer drugs equal less care, especially with a practice change that many other survivors in their metastatic support network did not experience. A patient’s quality of life can be worse with numerous and toxic side effects, and the dose may have to be reduced. A goal with metastatic breast cancer care is to control the disease and provide the best quality of life for the patient. Single-agent treatment lowers the risk of side effects, may improve the patient’s quality of life, and does not endanger overall survival. ASCO points out that combination chemotherapy can be advantageous and worth the chance of increased side effects when the cancer burden needs to be controlled because of severe or life-threatening symptoms.
- “Avoid using PET or PET-CT scanning as part of routine follow-up care to monitor for a cancer recurrence in asymptomatic patients who have finished initial treatment to eliminate the cancer unless there is high-level evidence that such imaging will change the outcome.”
Navigators need to be aware of this suggestion because routine PET/CT scans will not be a part of a survivorship care plan for an asymptomatic patient. The key is “asymptomatic.” Part of the survivorship plan will be to educate patients on persistent symptoms or pain that cannot be explained by accidents, falls, or other mishaps that may have caused the discomfort. ASCO explains that these tests are useful to diagnose and stage patients, as well as to monitor a symptomatic patient’s response to treatment. Using them as a tool to monitor for recurrence does not improve outcomes. Unnecessary tests and or procedures can be done when a false-positive is read on a scan.
- “Do not use a targeted therapy intended for use against a specific genetic aberration unless a patient’s tumor cells have a specific biomarker that predicts an effective response to the targeted therapy.”
Targeted cancer therapies are drugs that obstruct defined molecules involved in cancer cell growth and survival. An example is tamoxifen that is given to an ER+ breast cancer patient. One would not use hormone therapy for an ER-patient. There are potential side effects with this treatment, so there is risk in their utilization for patients who do not display the target for the drug. Herceptin for HER2+ disease is another example. There are numerous targeted therapies that can benefit cancer patients if the patient has a specific biomarker in their tumor cells that makes them susceptible to the targeted agent.123
Future Breast Cancer Care
So what will the future bring in breast care? Definitely more Choosing Wisely suggestions, screening guidelines based on individual patient characteristics and family history, therapy based on tumor genetics, new interactive decision aids, and evolved treatment with fewer side effects. The theme of more or longer treatment being the avenue to the best survival outcomes will continue to be challenged.
Two abstracts from the 2013 San Antonio Breast Cancer Symposium using randomized prospective data demonstrated that removing the breast tumor in women who were diagnosed with metastatic breast cancer did not have a better overall survival than women who were treated with systemic therapy alone.124 The old retrospective series of this subset of patients with advanced breast cancer had suggested benefit from removing the primary tumor.124 So, the way of thinking has been challenged for women with metastatic breast cancer who have asymptomatic primary tumors, and other ongoing trials on this issue will provide an answer in the future.
What about the idea of breast cancer surgery with no incision, and no puncture wounds or blood loss? At the Radiological Society of North America Annual Meeting in 2013, a group of researchers from Rome described magnetic resonance–guided, focused ultrasound that ablated small breast cancers.125 The ablation took 2.5 hours–longer than lumpectomy surgerybut the recovery was a few days of edema and tenderness, and the treatment is completed under conscious sedation.124 The same technique that is used for nonsurgical ablation of fibroid tumors is being applied to women with a small, single focus of early-stage breast cancer.
All navigators are vital for patient and public advocacy and education on the changes in the practice of breast cancer management as we are witnessing a shift in breast cancer care treatment modalities to evidence-based, individualized, personal care. More is not always better, care is patient centered, and the primary focus of treatment is biologically and genetically based. The uniqueness of each patient, with the histopathology of their tumor, brings challenges to the healthcare team to treat holistically in a timely manner. Nurse navigators are key team members to help patients maneuver through the healthcare system, use community resources, and assist the patient in comprehending the treatment options and plan based on personalized pathology. All navigators play a role in patient and public advocacy, as well as education on the changes in the practice of breast cancer management.
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Breast Cancer - October 5, 2016
The Breast Cancer Index (BCI) test is a quantitative assay based on the expression of 11 genes that may help patients with estrogen receptor–positive (ER+), early-stage breast cancers, in consultation [ Read More ]
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