Medicine Essay Sample. Endocrine Therapy and Breast Cancer

PART 1: Lay article Facts about Breast Cancer

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Cancer is one of the diseases that account for several deaths across the world. In the previous times, the disease was misconceived as only affecting the wealthy due to their unhealthy eating habits and lack of activity. However, recent cases of cancer including prostate cancer, breast cancer, lung cancer, and several other types of cancer have awakened the researchers to conduct proactive research to determine the nature and spread of the disease (Heldring et al. 2007 p.926). Breast cancer is one of the most common types of cancer alongside cervical cancer that affects women throughout the world. Scientists have discovered that breast cancer starts in the inner linings of the milk duct or lobules that supply breast milk. Some deadly strains of breast cancer can spread to the other parts of the body. Proximate research on breast cancer has shown that an estrogen receptor pathway critically influences its development and progress. Based on this understanding of the role of estrogen receptor in breast cancer development and progression, research has been studied been undertaken to establish the ways to block it, but this attempt is limited by the intrinsic and acquired resistance of the system to any artificial controls (McBryan, 2015 p.5373).

Several proposals have been made to explain the causes of the estrogen system resistance to therapeutic control. These explanations include natural changes in the cell cycle, deregulation of some components of the estrogen receptor pathway and activation of the tumor escape pathway that makes the cells have an alternative way of growing excessively (McBryan, 2015 p.5374). The recognition of various factors causing estrogen resistance has led to numerous advancements in breast cancer treatment that specifically targets the ER and growth factor receptor signaling. These procedures have been determined to block the interactions between the two pathways thus eliminating the possibility of unchecked calcareous cell growth in the breast (Santen et al., 220 p.157). Nonetheless, the active application of the ER and growth receptor signaling medication for breast cancer depends on the appropriate prior identification of the right patients whose cancers can be better treated through the particular co-targeting strategies.

Endocrine therapy means the type of treatment which specifically targets the estrogen receptor by introducing an antagonist or preventing the tumor from receiving estrogen to block receptor binding. Some cases of breast cancer diagnosis and treatment, multigene tests are conducted on breast suspected to be infected with primary cancer (Santen et al. 2004 p. 339). This diagnosis helps in making decisions for adjuvant therapy. Nonetheless, in some cases, breast tumors become resistant to ER treatments. The breast cancers that manifests aggressively, undergoes drastic morphological transformations and are genetically unique are in most cases less responsive to ER treatments.

Mechanisms of Estrogen Operations Related To Resistance of ER-Targeted Treatments

The human body systems are organized to regulate internal processes while at the same time preventing external toxins from infiltrating. The activities of these systems are in such a way that keeps the cells active, offer resistance to toxins and overcome cellular stress. During the development and spread of cancer through a process called oncogenesis, the cancer cells exploit the established boy system to ensure a suitable environment for its proliferation (Santen et al., 2004 p. 337). Cancergenetically changes the normal body systems to achieve resistance to different forms of treatment. The estrogen signaling system is a primary biological cycle that regulates various functions including cell growth, apoptosis, and angiogenesis (Santen et al., 220 p.159). The breast cancer cells exploit the estrogen receptor system to offer a survival pathway against various established treatments. The breast cancer cells use the estrogen, which is a female hormone to induce resistance.

The primary function of the estrogen receptor that is related to the resistance of breast cancer cells is its genomic activity which involves altering the genes responsible for normal functioning of cells, growth, and survival of tumors. The estrogen controls the expression of various genes through the processes of up-regulation and down-regulation (Santen et al., 220 p.158). After binding with the estrogen, an estrogen receptor combines with another receptor monomer to attract multiple coactivators and corepressors to specific DNA sites. In this sense, the complex of ERs function as a regulator which is targeted by the breast cancer cells.

Clues on Resistance of breast cancer cells to Endocrine Therapy

Various clinical observations provide strong clues on the mechanism through which breast cancer become resistant to endocrine therapy (ET) (McBryan, 2015 p.5374). Patients who have undergone endocrine therapy experience a loss of estrogen receptors over time hence the progression of the tumors changes from being motivated by the estrogenic cycle to the escape pathways (Den, 2013). One cause related to survival of breast tumors is the up-regulation of human epidermal growth factor receptor 2 (HER2) which acquires gene amplification or overexpression (McBryan, 2015 p.5375). The HER 2 then takes over the role of allowing the developments of cancer by providing an alternative pathway through which the cells can grow or reduce the levels of estrogen receptors which renders the tumor less sensitive to estrogen.

Fig. 1.0: Cell line models of endocrine resistance (Source; Vareslija, McBryan et al., Clin Can Res 2016)

Preclinical studies and clinical data provide an explanation that there is a possibility that the activities of cancer can quickly shift from estrogen receptors to HER2. Therefore, any endocrine treatment targeting either of the two dominant pathways reignites the other (McBryan, 2015 p.5376). On the other hand, progesterone receptors (PR) are often lost more frequently than ER with endocrine treatments. With this loss in PR, the cancer cells become more aggressive with worse survival outcomes for patients.

Fig. 2.0. Targeting Estrogen in Breast Cancer (Source; Source; Vareslija, McBryan et al., Clin Can Res 2016)

Patients who undergo PR decline after a resistance on endocrine treatment have worse survival outcomes compared to those maintain the PR expression. Due to this positive relationship between breast cancer progression and PR reduction, it can be deduced that the latter is associated with increased growth factor signaling and up-regulation (McBryan, 2015 p.5375). Based on clinical observations, the resistance of breast cancer to endocrine treatment can take two primary forms. The primary form is de novo resistance while the second is acquired resistance to treatment. De novo resistance occurs before treatment is administered while the acquired resistance to endocrine treatment occurs during a particular period of response to cancer.

The use of ER for diagnostic and therapeutic purposes is often accomplished as an independent variable. However, targeting of the ER system through endocrine therapy separately from the rest of the cellular and tumor signaling networking results in increased incidences of tumor resistance (Den, 2013). Practical handling of breast cancer requires handling ER as a dynamic process instead of looking at is as a fixed variable for designing new treatment strategies for breast cancer patients.

References List

Heldring, N., Pike, A., Andersson, S., Matthews, J., Cheng, G., Hartman, J., Tujague, M., Strom, A., Treuter, E., Warner, M., and Gustafsson, J.A., 2007. Estrogen receptors: how do they signal and what are their targets. Physiological Reviews, 87(3), pp.905-931.

McBryan, J., Fagan, A., McCartan, D., Bane, F., Vare lija, D., Cocchiglia, S., Byrne, C., Bolger, J., McIlroy, M., Hudson, L., Tibbitts, P., O Gaora, P., Hill, A. and Young, L. (2015). Transcriptomic Profiling of Sequential Tumors from Breast Cancer Patients Provides a Global View of Metastatic Expression Changes Following Endocrine Therapy. Clinical Cancer Research, 21(23), pp.5371-5379.

Santen, R.J., Song, R.X., Zhang, Z., Yue, W. and Kumar, R., 2004. Adaptive Hypersensitivity to Estrogen Mechanism for Sequential Responses to Hormonal Therapy in Breast Cancer. Clinical Cancer Research, 10(1), pp.337s-345s.

Santen, R.J., Song, R.X., Zhang, Z., Kumar, R., Jeng, M.H., Masamura, S., Lawrence, J., MacMahon, L.P., Yue, W. and Berstein, L., 2005. Adaptive hypersensitivity to estrogen: mechanisms and clinical relevance to aromatase inhibitor therapy in breast

PART 2: Lay summary the McBryan Seminar Presentation

Throughout the world, cancer in its various types causes several deaths despite developments in treatment technologies. Breast cancer is the most common type of calcareous cells that causes health complications, especially among women. This health problem sometimes necessitates breast surgery that leads to a loss of the entire breast to prevent possible spread to other parts of the body (McBryan, 2015, p.5377). Therapeutic progress has been made to facilitate the diagnosis and treatment of the breast cancer, but challenges still exist with the management of this particular type of tumors. One innovative treatment for breast cancer in the current age, the endocrine therapy is one of the most recent achievements in the control of breast cancer, but the fact that the calcareous cells exploit alternative escape pathways to proliferate within the body systems pose a challenge to the effectiveness of the ET.

Recurrence of breast cancer is associated with the fact that breast cancer has the potential of shifting between the estrogen receptors to other body systems such as the progesterone cycle thus becoming malignant and resistant to possible treatments. Despite the fact that the causes of breast cancer residence to endocrine therapies is not very clear, clues pint to a possible existence of alternative progression pathways for the disease (McBryan, 2015, p.5374). Clinical research indicates that most breast cancers have a close association with the estrogen receptor (Acconcia, Barnes, and Kumar, 2006, p.1206). The association between the tumors and the estrogen receptors can be drawn from the fact that the tumors are steroid positive thus find the receptors conducive for their growth.

Fig. 3.0: Targeting the Estrogen Pathway (source: Breast cancer slid share retrieved from https://www.google.com/search?q=Targeting+the+estrogen+pathway&espv=2&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjq1MXJodLQAhVL7hoKHReuDwMQ_AUICCgB&biw=1366&bih=676#imgrc=PN4xIUa4rH_mOM%3A)

The research called Transcriptomic Profiling of Sequential Tumors from Breast Cancer Patients Provides a Global View of Metastatic Expression Changes Following Endocrine Therapy undertook to characterize the global expression changes that occur with the metastatic disease. The study pioneered the use of Ribonucleic acid (RNA) sequencing on matched primary, nodal and liver resistant tumors from patients treated with tamoxifen after a period of the diseases progression (McBryan, 2015, p.5375). The study proceeded with examining the expression of genes that were elevated in the metastases of sequenced patients in a broader spectrum of matched patient groups suffering from resistant tumors from different places. The xenograft model was used in vivo to investigate the impacts of the tamoxifen treatments on tumors that were resistant to endocrine treatments.

Fig. 4.0: The use of estrogen cycle to prevent breast tumors (Den Hollander, P., Savage, M. and Brown, 23 September 2013. Targeted Therapy for...