Course
Breast Cancer Updates
Course Highlights
- In this Breast Cancer Updates course, we will learn about modifiable and non-modifiable risk factors for breast cancer.
- You’ll also learn the disparities in breast cancer outcomes among different ethnic groups and socioeconomic statuses.
- You’ll leave this course with a broader understanding of current diagnostic and screening tools available for breast cancer.
About
Contact Hours Awarded: 1
Course By:
R.E. Hengsterman MSN, RN
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Introduction
In the United States, breast cancer stands as the most prevalent form of cancer among women, excluding nonmelanoma cancers of the skin [1] [4]. Breast cancer represents 30% (1 in 3) of all new cancer diagnoses in females per year [2]. While there has been a noted decrease in mortality rates, breast cancer continues to be a significant cause of cancer-related deaths among women, ranking as the second leading cause behind lung cancer [2].
In Hispanic women, breast cancer is the primary cause of cancer-related fatalities, while African American women exhibit higher mortality rates from breast cancer than women from other ethnic backgrounds [1] [3]. The American Cancer Society forecasts that, in 2024 within the U.S., 310,720 women will receive a diagnosis of invasive breast cancer, alongside 56,500 instances of ductal carcinoma in situ (DCIS), which is a non-invasive breast cancer variant. Estimates are that 42,250 women will die from breast cancer [2].
The disparities in access to care and health outcomes remains a critical challenge to ensure equitable health outcomes for all women. The prognosis for breast cancer varies based on geographic location, socioeconomic status, and race [3]. Women from minority groups and lower socioeconomic backgrounds often have lower survival rates, attributed to factors including later stage at diagnosis, differences in tumor biology, limited access to care, and disparities in treatment [3].
Self Quiz
Ask yourself...
- What are potential underlying factors contributing to the ethnic disparities in breast cancer outcomes?
- What strategies could address and bridge the gap in healthcare access and treatment outcomes for women from minority groups and lower socioeconomic backgrounds?
Statistical Evidence/Epidemiology
Breast cancer continues to be the most diagnosed cancer among women worldwide [5]. Current statistics underscore the widespread impact of this disease. Over the past four decades there has been a general increase in breast cancer incidence rates with an annual rise of 0.5% (2010-2019) [4].
In 2023 there was a significant increase in the number of new breast cancer cases [5]. The identification of cases at a localized stage, screening programs, greater awareness, lifestyle changes and the presence of hormone receptor-positive traits in tumors may be driving the escalation of cases.
Mortality rates from breast cancer have decreased 1.3% from 2011 to 2020 [4]. From 1989 to 2020, there was a 43% drop in the death rate from breast cancer equates to 460,000 fewer deaths attributed to the disease during this period [4]. The median age for breast cancer diagnosis is 62, indicating that half of the diagnosed women are 62 or younger at the time of their diagnosis [2]. A small percentage of breast cancer cases occur in women under the age of 45 [2].
The five-year survival rate for breast cancer has been improving for those diagnosed at an early stage. The American Cancer Society reports that the 5-year relative survival rate for localized breast cancer remains at 99 percent [6]. In cases where the cancer has extended to nearby structures or lymph nodes, the five-year relative survival rate is 86 percent [6]. Advances in targeted therapies and hormone treatments have played a crucial role in enhancing survival rates.
In the United States, cancer impacts all population segments, yet certain groups experience a higher burden of the disease due to factors such as social, environmental, and economic disadvantages [7]. These disparities in cancer, often referred to as cancer health disparities, manifest in various measures including the incidence of new cases, the prevalence of existing cases, mortality rates, survival rates post-diagnosis, morbidity from cancer-related health complications, and aspects of quality-of-life following treatment [7]. These disparities extend to the financial burden of cancer or related health conditions, variations in screening rates, and differences in the stage of cancer at the time of diagnosis.
Risk Factors for breast cancer include age (with higher risk as women get older), increased estrogen levels, genetic predisposition (mutations in the BRCA1 and BRCA2 genes), family history of breast cancer, lifestyle factors (alcohol consumption, obesity, and physical inactivity), and reproductive history (such as age at first menstruation and menopause) [8].
There are two classifications of risk factors for breast cancer: modifiable and non-modifiable. Non-modifiable risk factors include being female, older age, family history of breast or ovarian cancer, genetic mutations, race/ethnicity, factors related to pregnancy and breastfeeding, menstrual history and menopause, breast tissue density, previous breast cancer history, non-cancerous breast diseases, and prior radiation therapy [8].
Research indicates a correlation between greater height and a higher risk of breast cancer. Studies have found that women who are 69 inches (175 cm) or taller have a heightened likelihood of developing breast cancer compared to women who are shorter than 63 inches (160 cm) [9].
Modifiable risk factors comprise hormonal replacement therapy, exposure to diethylstilbestrol, physical activity levels, being overweight or obese, alcohol intake, smoking habits, insufficient vitamin supplementation, excessive exposure to artificial light, consumption of processed foods, exposure to certain chemicals, and the use of various drugs [8].
Women employed in night-shift roles face an increased risk of developing breast cancer compared to those who do not work during the night [9]. Although the precise reason for the elevated risk remains unclear, it may be associated with melatonin, a hormone produced at night [9].
Black women experience a five-year relative survival rate for breast cancer that is lower than all other racial and ethnic groups across every stage of diagnosis and for each subtype of the disease. The survival gap between Black and White women ranges from 6% to 8% for every subtype of breast cancer [4]. Women who have a first-degree relative with a history of breast cancer face a two to threefold increase in their own risk of developing breast cancer over their lifetime [11].
The potential impact of organochlorines, such as polychlorinated biphenyls (PCBs), dioxins, and organochlorine pesticides including dichlorodiphenyltrichloroethane (DDT), on breast cancer risk lacks the establishment of a definitive link [9].
Self Quiz
Ask yourself...
- Given the general increase in breast cancer incidence rates over the past four decades, how might the role of enhanced screening programs and greater public awareness have contributed to this rise?
- With the median age for breast cancer diagnosis being 62 and a notable proportion of cases occurring in women under 45, what implications does this have for screening recommendations and preventive measures across different age groups?
- What factors might contribute to disparities in breast cancer survival rates, and what strategies could be employed to address them?
- What preventive actions can providers recommend to women in relation to modifiable risk factors including lifestyle choices and environmental exposures?
Etiology/Pathophysiology
The etiology of breast cancer involves a multifaceted interaction of several risk factors. These include a previous breast cancer diagnosis, a family history of breast cancer, obesity, above-average height, smoking, alcohol use, early onset of menstruation, late menopause, a sedentary lifestyle, not having given birth, and the use of hormone replacement therapy [10]. Understanding these mechanisms is crucial for developing effective prevention, diagnostic, and treatment strategies.
Genetic mutations increase the risk of developing breast, ovarian, and several other types of cancer. The most well-known are mutations in the BRCA1 and BRCA2 genes, which increase the risk of breast and ovarian cancers. A woman carrying a BRCA1 or BRCA2 gene mutation faces a risk of up to 70% for developing breast cancer by the age of 80 [12]. Several other influential genes include the CHEK2, PTEN, TP53, ATM, STK11/LKB1, CDH1, NBS1, RAD50, BRIP1, and PALB2 which may have high or moderate penetrance, contributing to the susceptibility to breast cancer within the spectrum of hereditary breast cancer [13].
Estrogen and progesterone are key in the development of breast cancer. Women with early menarche, late menopause, and those who have taken hormone replacement therapy (HRT), or oral contraceptives may have a higher risk due to prolonged exposure to estrogen [14].
Lifestyle choices and environmental exposures impact breast cancer risk. Significant factors include diet, obesity, lack of physical activity, alcohol intake, radiation exposure, and certain environmental pollutants [8]. Women who first give birth after age 30, those who have never given birth, or those experiencing a late onset of their first menstrual period or early menopause, are at a heightened risk [15].
Self Quiz
Ask yourself...
- Considering the complex interaction of various risk factors in the etiology of breast cancer, such as lifestyle choices and genetic predispositions, how can this multifaceted understanding inform and refine the approaches to prevention and early detection of breast cancer?
- What are the implications for genetic counseling and testing in both high-risk individuals and the general population?
- How do the roles of estrogen and progesterone in breast cancer development risk factors shape the recommendations for breast cancer screening and preventive strategies in women with different reproductive histories and hormonal exposures?
Pathophysiology
Breast cancer originates from DNA damage, genetic mutations, exacerbated by exposure to estrogen [11]. In certain cases, individuals may inherit DNA anomalies or genes predisposing to cancer, such as BRCA1 and BRCA2 [11]. These mutations lead to uncontrolled cell growth and division. Over time, these cells can invade nearby tissues and spread (metastasis).
Breast cancer is not a single disease, but a group of diseases differentiated by the presence of hormone receptors (estrogen and progesterone) and the HER2 protein [16]. The primary subtypes include hormone receptor-positive (HR+), HER2-positive, and Triple-negative disease, which lacks the expression of estrogen, progesterone, and HER2 receptors [16].
The tumor microenvironment (TME) is critical in the development and dissemination of cancer [16]. This ecosystem surrounding a tumor comprises proliferating tumor cells, immune cells, blood vessels, and stromal cells, with its composition varying across different tumor types. As a tumor enlarges, cancer cells can invade adjacent tissues and structures, a process known as invasive cancer.
When these cells spread to distant body parts, this is termed metastasis. During metastasis, cancer cells detach from their original site, travel via the blood or lymphatic system, and form new tumors elsewhere [11]. Common sites of metastasis include the spinal bones, lungs, and liver. Certain subtypes, such as triple-negative and HER2-positive breast cancers, are also known to metastasize to the brain [19].
Self Quiz
Ask yourself...
- How does understanding the role of inherited genetic anomalies, such as BRCA1 and BRCA2 mutations, impact the strategies for screening and early intervention in individuals at increased genetic risk?
- Considering the diverse nature of breast cancer, categorized into subtypes like Hormone receptor-positive, HER2-positive, and Triple-negative, how does the variability in the tumor microenvironment across these subtypes influence the development of targeted therapies and personalized treatment approaches?
Diagnostic and Screening tools
The current landscape of breast cancer diagnostic and screening tools reflects a combination of well-established methods including mammography and ultrasound, along with emerging technologies and precision medicine approaches. Full-field digital mammography (FFDM) captures mammogram images for easier storage and enhanced analysis and beneficial for women with dense breast tissue [21].
3D Mammography (Tomosynthesis) offers a more sophisticated approach by creating three-dimensional images from multiple X-rays taken at various angles, proving effective in dense breast tissue [22]. Breast Ultrasound employs sound waves to visualize internal breast structures [22]. Additional diagnostic options include breast MRI (Magnetic Resonance Imaging) utilized alongside mammography for high-risk individuals, such as those with a significant family history of breast cancer or known genetic mutations like BRCA1 or BRCA2 [22] [23].
Various biopsy techniques can identify breast abnormalities. Ultrasound-Guided Biopsy locates the area of concern using ultrasound [59]. Stereotactic Biopsy utilizes mammography for precise needle guidance when the abnormal area is not visible on ultrasound [59]. If an MRI reveals a suspicious location, conducting an MRI-guided biopsy becomes crucial to ascertain if the finding is benign or malignant through histopathological analysis [24].
The impact of genomics on breast cancer treatment guides adjuvant treatment choices in early-stage cases and for breast cancers with HER2 overexpression, regardless of the stage. Genomic tests including Oncotype DX, PAM50 and MammaPrint analyze genes in breast cancer cells to assess recurrence risk, playing a crucial role in shaping treatment strategies [25].
Self Quiz
Ask yourself...
- How do advancements in breast cancer diagnostic tools, such as Full-field Digital Mammography and 3D Tomosynthesis, and their effectiveness in dense breast tissue, contribute to the early detection and accurate diagnosis of breast cancer?
- How do biopsy techniques like Ultrasound-Guided Stereotactic, and MRI-Guided Biopsies complement each other in ensuring a comprehensive evaluation and accurate diagnosis of breast abnormalities
- How do genomic tests influence the decision-making process for adjuvant treatments in early-stage breast cancers and those with HER2 overexpression?
Medication Management
Within the multifaceted scope of breast cancer treatment, an array of therapeutic approaches, including Hormone Therapy, Chemotherapy, Targeted Therapy, and Immunotherapy, play pivotal roles. Surgery, radiation, chemotherapy, hormone therapy, and targeted therapy form the core pillars of breast cancer treatment.
For hormone receptor-positive breast cancers in both premenopausal and postmenopausal women, therapies include Tamoxifen, Aromatase Inhibitors, and Selective Estrogen Receptor Degraders (SERDs) including Fulvestrant [27].
Chemotherapy, using cytotoxic agents including Anthrocyclines, Taxanes, Alkylating Agents, and Platinum Agents are vital for aggressive or advanced-stage breast cancers, including triple-negative and BRCA-mutated types [30]
Targeted therapy drugs, including HER2-Targeted Therapies for HER2-positive breast cancers, CDK4/6 Inhibitors for hormone receptor-positive, HER2-negative breast cancer, PI3K Inhibitors for PIK3CA-mutated cases, and PARP Inhibitors for BRCA1 or BRCA2 mutations, focus on specific cancer cell characteristics [31].
Immunotherapy, including Checkpoint Inhibitors such as pembrolizumab and atezolizumab, enhances the immune system’s response against certain advanced breast cancers, including triple-negative types [32]. Triple-negative breast cancer (TNBC) represents about 15–20% of breast cancer cases and is unique as the only subtype without a specific targeted treatment [33].
Evolving treatments highlight the effectiveness of a specific drug combination in treating metastatic breast cancer among younger women. The FDA approved treatments for advanced or metastatic breast cancer in conjunction with hormone therapy include Palbociclib (Ibrance), ribociclib (Kisqali), and everolimus (Afinitor) [34].
Ribociclib, in particular, has demonstrated increased survival rates in metastatic breast cancer patients and, when paired with hormone therapy, has slowed the progression of the disease in younger women [35].
The U.S. Food and Drug Administration (FDA) has sanctioned the use of elacestrant (Orserdu) for treating estrogen receptor-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer in postmenopausal women or adult men [36].
Abemaciclib (Verzenio) is effective in treating advanced or metastatic HR-positive, HER2-negative breast cancer, both during and subsequent hormone therapy.
As of October 2021, Abemaciclib (Verzenio) in conjunction with hormone therapy is a treatment option for selected early-stage cases after surgery [37]. Alpelisib (Piqray) has received approval for use alongside hormone therapy in treating advanced or metastatic HR-positive, HER2-negative breast cancers that have a PIK3CA gene mutation [38].
Sacituzumab govitecan-hziy (Trodelvy) is employed in the treatment of HR-positive and HER2-negative breast cancer in cases where the cancer has metastasized or is inoperable through surgery [39]. This therapeutic option is for individuals who have received hormone therapy and at least two other forms of treatment. Sacituzumab govitecan-hziy (Trodelvy) may enhance both progression-free survival and overall survival [39].
Self Quiz
Ask yourself...
- How do the various therapeutic approaches in breast cancer treatment, such as Hormone Therapy, Chemotherapy, Targeted Therapy, and Immunotherapy, complement each other in managing different subtypes and stages of breast cancer?
- Given the lack of a specific targeted treatment for Triple-Negative Breast Cancer (TNBC), what are the current strategies and ongoing research efforts aimed at finding effective treatments for this subtype?
- Considering the recent FDA approvals of drugs like elacestrant (Orserdu), abemaciclib (Verzenio), and alpelisib (Piqray) for specific breast cancer subtypes and stages, how do these advancements impact the overall prognosis and treatment options available to patients with advanced or metastatic breast cancer?
HER2-Positive Breast Cancer
The U.S. Food and Drug Administration (FDA) has authorized several targeted therapies for the treatment of HER2-positive breast cancer including Trastuzumab (Herceptin) for preventing relapse in early-stage HER2-positive breast cancer patients [42]. Pertuzumab (Perjeta) in metastatic HER2-positive breast cancer treatment, both pre-surgery (neoadjuvant) and post-surgery (adjuvant therapy) [43].
A combination of Trastuzumab and Pertuzumab can be employed with chemotherapy to prevent relapse in early-stage HER2-positive breast cancer and in metastatic disease. For advanced or metastatic HER2-positive breast cancer patients who have undergone prior HER2-targeted treatments, Trastuzumab Deruxtecan (Enhertu) [44].
In cases of inoperable or metastatic HER2-positive breast cancer, Tucatinib (Tukysa) alongside trastuzumab and capecitabine (Xeloda) shows effectiveness in instances with brain metastases owing to its capacity to penetrate the blood-brain barrier [45]. For patients with HER2-positive advanced or metastatic breast cancer, Lapatinib (Tykerb) in combination with capecitabine or letrozole [46].
The use of Neratinib Maleate (Nerlynx) in early-stage HER2-positive breast cancer and, in some circumstances, in conjunction with capecitabine (Xeloda) in advanced or metastatic disease [47]. For metastatic HER2-positive breast cancer patients who have received trastuzumab, Ado-trastuzumab Emtansine (Kadcyla) is a treatment option [48].
Self Quiz
Ask yourself...
- How does the availability of multiple targeted therapies, each with specific indications such as Trastuzumab (Herceptin), Pertuzumab (Perjeta), and Trastuzumab Deruxtecan (Enhertu), enhance the treatment landscape for HER2-positive breast cancer at various stages, from early-stage to advanced or metastatic disease?
- Considering the unique ability of Tucatinib (Tukysa) to cross the blood-brain barrier and its effectiveness in HER2-positive breast cancer with brain metastases, how does this advance the management of metastatic breast cancer in addressing difficult-to-treat complications?
HER2-Low Breast Cancer
A subtype of breast cancer, termed HER2-low, encompasses over half of all metastatic breast cancers [40]. The presence of lower levels of the HER2 protein on the surface of the tumor cells characterizes this subtype. In the past, categorized as HER2-negative, these tumors were unresponsive to treatments targeting the HER2 protein. In a clinical trial, trastuzumab deruxtecan (Enhertu) demonstrated an improvement in survival rates for patients with HER2-low breast cancer when compared to standard chemotherapy [49].
Self Quiz
Ask yourself...
- Given the recent clinical trial findings showing trastuzumab deruxtecan (Enhertu) improves survival rates in HER2-low breast cancer, a subtype considered unresponsive to HER2-targeted treatments, how might this change the approach to diagnosing and treating breast cancer subtypes that demonstrate lower levels of HER2 protein?
Triple-Negative Breast Cancer Treatment (TNBC)
Triple-negative breast cancers (TNBC) are difficult to treat due to the absence of both hormone receptors and HER2 overexpression and do not respond to targeted therapies. Chemotherapy remains the primary treatment approach for TNBC [50].
Emerging treatments including: Sacituzumab Govitecan-hziy (Trodelvy), Pembrolizumab (Keytruda) approved for use alongside chemotherapy in patients with advanced or metastatic disease, PARP Inhibitors including Olaparib (Lynparza) and Talazoparib (Talzenna) for treating metastatic HER2-negative or triple-negative breast cancers in patients with a harmful inherited BRCA gene mutation [51] [52]. Olaparib for certain early-stage HER2-negative or triple-negative breast cancer patients [53].
Self Quiz
Ask yourself...
- Considering the limitations of traditional treatments for Triple-Negative Breast Cancer (TNBC) due to the absence of hormone receptors and HER2 overexpression, how do emerging treatments like Sacituzumab Govitecan-hziy (Trodelvy) and Pembrolizumab (Keytruda) represent a shift in the treatment paradigm for patients with advanced or metastatic TNBC?
- With the approval of PARP Inhibitors like Olaparib (Lynparza) and Talazoparib (Talzenna) for metastatic HER2-negative or triple-negative breast cancers in patients with BRCA gene mutations, how might testing for BRCA mutations influence treatment decisions and outcomes for these specific subtypes of breast cancer?
Common Misconceptions
Addressing misconceptions is crucial to promote accurate breast cancer awareness and encourage appropriate screening and treatment. Dispelling myths can empower patients to make informed decisions about their health and reduce anxiety or stigma associated with the disease.
The prevalent misconceptions about breast cancer include:
Misconception: Only women can get breast cancer.
Reality: Men can develop breast cancer. In the United States, the lifetime probability of developing breast cancer stands at 1 in 833 for men and 1 in 8 for women [41].
Misconception: A lump in the breast always indicates breast cancer.
Reality: Not all breast lumps are cancerous. Many lumps are benign conditions including cysts or fibroadenomas. However, any new or changing lump in the breast requires evaluation by a healthcare professional.
Misconception: If you have no family history of breast cancer you will not get breast cancer.
Reality: While a family history of breast cancer can increase risk, the majority of breast cancer cases occur in women without a known family history [53]. Lifestyle factors, environmental exposures, and genetic mutations that are not familial can also contribute to breast cancer risk [8].
Misconception: Wearing underwire bras or using antiperspirants causes breast cancer
Reality: There is no scientific evidence to support the claim that underwire bras or the use of antiperspirants increase the risk of breast cancer [54].
Misconception: Mammograms can cause breast cancer to spread
Reality: Mammograms, which use low-dose X-rays to screen for breast cancer, do not cause cancer to spread [55]. The benefit of early detection through mammography far outweighs the minimal risk from radiation exposure [55].
Misconception: Breast cancer is always hereditary
Reality: Most breast cancers are not hereditary. Only about 5-10% of breast cancer cases are hereditary, resulting from mutations in genes such as BRCA1 or BRCA2 [12] [13].
Misconception: Young women do not get breast cancer
Reality: While the risk increases with age, young women can and do get breast cancer [56]. It is important for young women to be aware of their breast health and report any changes to their healthcare provider. In the United States, 1 in 196 adolescents and young adults between the ages of 15 to 39 receive a diagnosis of invasive breast cancer [56].
Misconception: Removing the entire breast improves your chance of survival when compared to a lumpectomy with radiation
Reality: Studies have shown that lumpectomy followed by radiation is as effective as a mastectomy for many women with early-stage breast cancer [57].
Misconception: Breast cancer is always a painful disease
Reality: Breast cancer does not always cause pain in the initial stages. The absence of pain does not mean the absence of disease [58].
Self Quiz
Ask yourself...
- How does addressing the misconception that only women can develop breast cancer, and recognizing that men also have a risk (albeit lower), alter the approach to breast cancer awareness and screening in the general population?
- In what ways can dispelling the myth that breast cancer is always hereditary, and acknowledging the link to genetic factors like BRCA1 or BRCA2 mutations, impact public understanding and the emphasis on regular screening for all individuals, regardless of family history?
- Given the common misconception that a lumpectomy with radiation is less effective than a mastectomy for treating early-stage breast cancer, how can accurate information about the equivalency of these treatments in terms of survival rates influence treatment decisions and patient perspectives on surgical options.
- How does the increased emphasis on prevention and the growing prominence of genetic testing and counseling for genes like BRCA1 and BRCA2, transform the approach to breast cancer management, development of individualized treatment plans, and family risk assessment strategies?
Conclusion
An intensified focus on prevention, including lifestyle factors such as diet, exercise, and alcohol intake continue to define the landscape of breast cancer [8]. Public health initiatives include educating women about modifiable risk factors, coupled with the importance of consistent screening.
The significance of genetic testing and counseling has risen to prominence. With the known BRCA1 and BRCA2 genes and the associated risk, a growing number of women are pursuing genetic testing [12]. This trend is pivotal for tailoring individual treatment strategies and informing at-risk family members.
References + Disclaimer
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