**Table 4.**

*Breast cancer phenotype-gene correlation [32–36].*


**Table 5.**

*Breast cancer testing considerations [20, 37].*

(1) MammaPrint uses 70 genes to test for prognosis and the adjuvant therapy susceptibility and (2) Oncotype DX Breast Recurrence Score Test uses a 21 gene scoring system to determine cancer recurrence, cancer aggression, and susceptibility to adjuvant therapy [20]. All of these tests provide a different function/use in testing that varies from identifying if cancer is present at all to specific breast cancer variants, instability, fusion of DNA, and/or identifying specific markers that make the cancer cells more susceptible and responsive to adjuvant treatment modalities [20]. The most advanced tests identify the rearrangement of chromosomal intergenic fusion (see **Table 5**). Both types of genetic mutations, germline and somatic can be individually fused or a mix of both and can be found in later stages of metastatic cancers [20]. Specific fusions are associated with molecular subtype ER+ metastatic cancers in the later cancer stages [20]. One promising test that can be done with NGS is to profile the cancer and its susceptibility of adjuvant therapy for cell-free DNA (cfDNA) found in plasma [37]. Circulating tumor DNA (ctDNA) are also found in plasma and helps to determine the risk of recurrence of cancer after remission [38].

The type of biomarkers and molecular subtypes play a significant role in the tumor growth and prognosis of this type of breast cancer (see **Table 6**).

Early detection/diagnosis of breast cancer is crucial in determining treatment plans and improving the chance for a positive response to treatments to achieve remission. Those that are diagnosed with a localized early-stage breast cancer (in situ) is 66% [10]. The five-year survival rate for the different stages when diagnosed is as follows: localized breast cancer = 99%, regional breast cancer = 86%, and distant breast cancer = 30% [10]. Invasive breast cancer is cancer that has spread through the blood or lymph nodes to other parts of the body, also known as metastasis. The percentage of breast cancers that are invasive is 83% [10]. This number is alarming and the advancements in targeted gene and immunotherapy are new tools in fighting breast cancer and improving survival rates [10, 20].

#### **5.2 Treatment options**

Traditional cancer treatments are chemotherapy, radiation therapy, hormone blocking therapy, and surgery (lumpectomy or mastectomy). Patients with a mastectomy may consider breast reconstruction surgery and should discuss this with their surgeon about when would be the best time to undergo this type of procedure based on their treatment plan [10]. Chemotherapy and hormone therapy has been around for a long time; however, the next promising therapies to impact treatment


#### **Table 6.**

*Breast cancer biomarkers and molecular subtypes [10].*

modalities include non-viral targeted gene therapy and immunotherapy. These cutting edge therapies joined the fight against breast cancer as adjuvant therapy, usually in combination with traditional therapies [10]. In pursuit of treating patients with the most effective treatment allowed, one such newcomer over the last few years has been precision therapy where oncogene drivers are used in individualized treatments using the molecular makeup of the patient to combat cancer cells with targeted gene therapy [20]. The impact of molecular subtypes on treatment and patient outcomes is reflected in **Table 7**. Immunotherapy is an innovative approach in fighting breast cancer by using one's own immune system to target and kill cancer cells. This type of therapy is called checkpoint inhibitors and is being used for TNBC.

The molecular subtype represents the hormone receptor status for estrogen, progesterone, and human epidermal growth receptor 2 (HER2). Based on the hormone receptor affinity, you can see the correlation for subtype, the Ki-67 recurrence predictor for cell division/replication, prognosis, therapy type, and treatment options. TNBC has the poorest prognosis, but recent clinical trials have proved positive in slowing the progression of metastatic or recurring TNBC, although some side effects are worse than traditional therapies. Sacituzumab Govitecan (Trodelvy) is a drug approved by the FDA in 2021 and is showing great promise for TNBC patients [41].

There are other new innovative research studies that have found that breast cancer stem cells (CSC) can achieve apoptosis with the use of specific PDE4 inhibitors (antiinflammatory medications) [42]. One study found that there is a signaling pathway to turn on cancer stem cells to survive through upregulation of PI3K/AKT/mTOR which increase CSC levels and in turn increases PDE4 levels. If these pathways can be turned on then they can be turned off. In turning off the pathway, it can stop the cyclic adenosine monophosphate (cAMP) from binding to regulatory subunits of inactive protein kinase A (PKA); thereby, stopping the conversion to an active form of (PKA) to trigger AKT and mTOR. Turning off this pathway will turn on autophagy of CSC and lead to cell death of the cancer cell. This cascade of signaling pathways is crucial


**Table 7.**

*Molecular subtypes on treatment and outcomes [20, 39, 40].*

in stopping phosphatidylinositol-3-kinase (PI3K) from proliferating CSC growth. CSCs were found to have elevated PDE4 levels when compared to healthy stem cells. Thus, the use of PDE4 inhibitors may hold the key to the downregulation of PI3K/ AKT pathway, thus reducing resistance to chemotherapy in CSCs [42]. This study found that PKA and cAMP levels antagonized the signaling pathway "PI3K/AKT/ mTOR" and caused "cell cycle arrest" [42].

## **5.3 Breast cancer incidence, mortality rate, and the disparity gap**

The disparity gap for breast cancer incidence is not what one might expect with Caucasians having the highest breast cancer incidence rate followed by Black women per every 100,000 women in the United States (see **Table 8**). The mortality rate is similarly surprising with Asian women having the lowest mortality rate and Hispanic women having the second lowest mortality rate compared to Caucasian women with the third lowest mortality rate, whereas Black women had the highest mortality rate. Accordingly, between 2012 and 2018, there was a 9% disparity gap between Black women compared to Caucasian and Asian Pacific Island women for a 5-year relative survival rate, 83% vs. 92%. This difference in survival rate translates into more


**Table 8.**

*Breast cancer incidence and mortality rates by ethnicity in the US from 2016 to 2020 [10].*

*Breast Health and Preventive Screening DOI: http://dx.doi.org/10.5772/intechopen.112597*

deaths in black women across the spectrum due to differences in access to care and insurance coverage/financial ability to pay for treatments [10]. The disparity gap for breast cancer survivors with late-stage breast cancer (stage 4) has begun to decrease steadily. This disparity gap has been zeroed out among racial/ethnic groups as a result of the Medicaid expansion programs implemented over the last couple of years [10]. Survival rates that are consistent with the elimination of disparity gaps will continue to take time, but as noted in late-stage breast cancers, this too is achievable.

Five percent of breast cancer survivors will face the daunting diagnosis of cancer once more after remission. When looking at the recurrence of breast cancer in women, there is a 70% chance that it will be in the opposite breast (contralateral). One study's findings reported that black women had a 44% greater chance of this recurrence whereas Hispanic women had an 11% greater chance of the same recurrence in the opposite breast compared to their Caucasian counterparts [10].

## **6. Conclusion**

The breast, in many ways, defines a young girl's journey into womanhood, motherhood, and old age, ever changing along the way [1]. With older age being one of the main risk factors for breast cancer and the changes that come with aging, it provides insight into the body's own shortcomings physically and genetically. Breast cancer impacts patients in many ways: physically, financially, emotionally, and functionally; however, advanced technologies in genomics through mapping of the human genome, nextgeneration sequencing, and evidence-based treatments all combined is helping to unlock the mystery of many disease processes, including breast cancer. This innovative science is changing the course of how we see, treat, and think about patient care, outcomes, and what is possible. The more we learn, the more impact we can have on patient care, treatment plans, and improved patient outcomes. We are on the cusp of a new scientific era, but new advancements in breast cancer treatments are still needed to continually strive to cure cancer for today's cancer patients and future generations to come [20].

#### **Conflict of interest**

The authors declare no conflict of interest.

#### **Author details**

Tammy Walker-Smith Texas A&M University Corpus Christi, Corpus Christi, TX, United States of America

\*Address all correspondence to: tammy.walker-smith@tamucc.edu

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
