Scenario: Kate is a 17 year old teen who has recently been diagnosed with the early stages of estrogen receptor positive and progesterone receptor positive breast cancer. To get any sort of breast cancer at this age is extremely rare. As she is pretty young, her parents were the ones who decided what treatment was best for her and what she should receive. After getting surgery, her doctor, Dr. Kim (me), also highly recommended Kate to get some sort of hormonal cancer treatment. Today is Kate’s appointment with Dr. Kim. However, this time Kate decides to pick a treatment for herself since it involves her hormones. She also decides to ask some questions during her visit. Doctor: Hello Kate! How are you feeling? Kate: I am feeling much better, thank you. Doctor: That’s very good to hear! So I heard you have some questions about the next step: hormonal cancer treatment. Well, feel free to ask away anything you want!Kate: Okay, thank you so much by the way.Doctor: Oh no problem! Kate: Alright so the first question I have is: What are hormones exactly and how do they affect breast cancer?Doctor: That’s a great question! So hormones are natural chemical substances flowing through our bloodstream that help different parts of our body to communicate with each other. They are created by glands from the endocrine system in our bodies that help function many organs and cells throughout growth. The primary source of hormones comes from the ovaries in women and testes in men. Normally, hormones have a positive effect on the body such as regulating different functions like menstruation. In fact, these hormones are typically used to stimulate or inhibit the process of producing proteins. However, cancer cells are still vulnerable to these hormone signals. Because of this, hormones can affect breast cancer cells by causing the cancer to grow. Two types of hormones that are commonly known for causing breast cancer among women include estrogen and progesterone. They do so by feeding the breast cancer through receptors called estrogen receptors or progesterone receptors. There are 4 different types of breast cancer. Two of the four are hormone dependent. If a breast cancer site is estrogen receptor positive (ER+) or progesterone receptor positive (PR+), they are hormone dependent. This means that they rely on the production of hormones for nutrients and development by attaching to the estrogen or progesterone with their receptors. Pathologists test whether or not you have hormone receptors on your cancer cells to check whether they can give you hormonal cancer treatments or not. On the other hand, estrogen receptor negative and progesterone receptor negative cancers are not affected by hormones whatsoever. Here, look at figure 1. As you can see, the target cells without receptors aren’t affected by the secreting cell. Meanwhile, the cell with the receptor is taking the hormones from the secreting cell. Usually, 2 or 3 breast cancers are hormone receptor positive just like your breast cancer. In fact, 80% of breast cancers are estrogen receptor positive. 65% of breast cancers are both estrogen and progesterone receptor positive. 13% of breast cancers are estrogen receptor positive and progesterone receptor negative. 2% of breast cancers are only progesterone receptor positive. Kate: Oh wow. I never knew that much about hormones and breast cancer itself! At least now I know what is causing this horrible cancer I have. So, what is hormonal cancer therapy?Doctor: Yeah, it really is terrible that you got diagnosed at such a young age. To answer your question though, hormonal cancer therapy, also known as hormone therapy, hormone treatment, anti-hormone treatment, and endocrine therapy, is a systemic therapy that can treat hormone receptor positive cancers by slowing them down or stopping them completely. It is the process in which estrogen is prevented from reaching the estrogen receptors. By doing so, the cancer cell will starve and will not be able to grow any further. This happens when the hormone is prevented from reaching and binding with the hormone receptors through the hormone treatments. Hormonal therapy lowers the risks of regrowth and the risk of getting breast cancer. It helps shrink and slow the growth of advanced stage or metastatic hormone receptor positive breast cancers, cancers that can spread to other parts of the body from the primary site. Kate: Hm.. interesting… What different types are there? How do they affect you? How do they work against cancer?Doctor: Hormonal cancer therapies are performed through either one or both of two methods; blockers and inhibitors. Blockers completely prevent the binding of the hormone and the hormone receptor positive cancer while inhibitors initially prevent the production of hormones, specifically estrogen. Blockers can also change and interfere with the whole behavior process of these hormones in our bodies through these treatments. Examples of a hormonal treatment are Selective Estrogen Receptor Modulators (SERMs). The most commonly used SERM is a pill known as tamoxifen. This hormone treatment pill changes the shape of the estrogen receptors openings and selectively blocks estrogen from telling cancer cells to grow. It prevents the possibility of breast cancer growth in the other breast, invasive breast cancer, and the cancer growing back in the original breast by 50%. Tamoxifen can benefit those who have a high risk of cancer. They can also slow and stop the cancer from spreading and forming more tumors in other parts of the body for those who already have this type of cancer. These drugs can actually increase your chances of living longer. In addition, by selectively blocking the estrogen from reaching cancer cells, the gene expression and the behavior of these cells change, preventing proliferation and the growth of a tumor. This precise mechanism regarding how these drugs can selectively pick a subunit of a whole group is not yet known. Although tamoxifen is a great treatment used to fight against breast cancer cells, this type of treatment can actually increase the potential risk of getting uterine cancer by providing the uterus with more estrogen. It also acts as anti-estrogen in bone cells. Another example of a Selective Estrogen Receptor Modulator is Evista (raloxifene). Raloxifene can decrease estrogen activity in both the breast and the uterine tissues. It also does not affect endometrial growth, a common site of cancer. Both tamoxifen and raloxifene have the same benefits in the breast through the interference of estrogen when it enters a targeted cell, however, the raloxifene has better improved side effects. The last Selective Estrogen Receptor Modulator is toremifene (fareston). Toremifene is like tamoxifen but it is only approved to be used on metastatic breast cancers. It is not likely to be used if tamoxifen was already previously used on a patient. Kate: And what do the inhibitors do? Doctor: Hormone inhibitors and down regulators reduce the body’s hormone production. Estrogen receptor down regulators prevents cancer by lessening the activity and concentration of these receptors. One specific inhibitor that is most commonly used is the aromatase inhibitor (AI). Aromatase is an enzyme made by proteins and fat cells that is used to convert androgen into estrogen through parts in your bodies called androgen precursors. Androgen is a sex hormone mostly found in males. However, females have them too. This androgen hormone is produced by two glands called adrenal glands that sit atop of your kidneys. By blocking aromatase, AI’s prevent the production of a certain type of estrogen known as estradiol. Kate: All of this sounds so complicated yet I am still sort of intrigued and fascinated by it. How do I know whether to receive a blocker or an inhibitor?Doctor: Well, one thing I want to mention that I have not previously is about who can receive what type of hormone treatment. Tamoxifen and raloxifene are popular among women with early stages of breast cancer or premenopausal women, women who have not gone through menopause. Inhibitors are recommended for postmenopausal women. This is because women who have gone through menopause no longer rely on their ovaries for a source of hormones including estrogen since their ovaries have been shut off. For this reason, their bodies resort to the adrenal glands and aromatase for the natural hormones. In fact, aromatase inhibitors should only be used for postmenopausal women because they can actually increase estrogen and hormone levels in premenopausal breast cancer patients with hormone receptor positive cancers. This happens because the aromatase inhibitors don’t affect and stop the ovaries from producing estrogen. If you want to take aromatase inhibitors because you think they are the best and most effective option for you, there are special treatments that can make you temporarily or permanently postmenopausal. These treatments are called ovarian suppression. Ovarian suppression is a process in which the ovaries are shut down making a woman postmenopausal. There are three different methods a premenopausal woman can take to remove or shut down her ovaries to treat metastatic breast cancer or the early stages of breast cancer. The first one is called oophorectomy or ovarian ablation. In this process, the ovaries are permanently removed. The second option is something called luteinizing hormone release hormone (LHRH) analogs. This is a drug that sends signals to the ovaries to temporarily stop functioning and produce estrogen. The last option is known as chemotherapy drugs. These drugs also signal the ovaries to stop producing estrogen. However, this drug may make a woman either temporarily or permanently postmenopausal depending on the woman’s ovaries and her functions and damages. Although these treatments have the risk of becoming postmenopausal permanently, it allows a broader window of hormonal treatments, such as AI’s, to open up. Kate: Where is hormonal therapy received? What place of your body?Doctor: It depends on which treatment you are getting. Hormonal therapy can be received orally, as injections, or during surgery. Injections are placed in muscles in your arms, thighs, or your hips. Surgery is performed by removing organs that produce hormones like ovaries or testicles. LHRH analogs are given by injections under the skin in your stomach area. Tamoxifen and aromatase inhibitors are ingested as drugs or pills. Kate: Hm thank you. Oh, actually I also wanted to ask, what are the side effects?Doctor: Well, each different hormonal cancer treatment comes with different side effects. Side effects will probably be seen mostly in your bones, cholesterol level, and your overall well-being. This is because estrogen actually helps your bones gain strength, keeps your cholesterol low, and improves your sense of well being. Since hormonal cancer treatments reduce the production of estrogen, the other estrogen dependent parts of your body will obviously be negatively affected. This is not the only side effect, however. Common side effects of tamoxifen include hot flashes, vaginal discharge, irregular menstrual periods, thinning bones, headaches, mood swings, fatigue, vomiting, vaginal dryness or itching, irritation of the skin around the vagina, and skin rash. Rare side effects of tamoxifen are blood clots in the legs or lungs, strokes, uterine cancer, and cataracts that can develop pain, redness, swelling, chest pain, and shortness of breath. Next, side effects of LHRH analogs include hot flashes, headaches, weight gain, thinning bones, and bone pain. Aromatase inhibitor side effects are hot flashes, nausea, vomiting, muscle pain, joint stiffness, and painful bones or joints. Serious side effects of aromatase inhibitors include cholesterol increase and thinning bones which may lead to osteoporosis or fractures. There are drugs, however, such as bisphosphonates or denosumab that are used to strengthen bones when this side effect comes into play when using AI. For women who have cancer that has spread to their backs, side effects include soreness, pain, uncontrollable high calcium levels, and swelling in the muscles and bones called tumor flares. Side effects and symptoms of ovarian suppression include hot flashes, night sweats, mood swings, and vaginal dryness. Most of these treatments also all have side effects on pregnancy, sexual functions, satisfaction/pleasure, and sexual dysfunction. Some treatments can also result in diarrhea, enlarged and tender breasts, and possibly weight gain or weight loss. In addition, one important piece of information to note is that side effects can differ depending on gender, what type of therapy you receive, and how your body reacts to the therapy. Kate: How does hormone therapy work with other treatments?Doctor: That’s a great question! Hormone therapy is actually used as an adjuvant or neoadjuvant therapy meaning that it is used before or after other treatments to ensure that the cancer won’t grow back or spread to other parts of the body. It can be used with, after, or before chemotherapy, surgery, and radiation therapy. Since you got surgery, these hormonal treatments will make sure that your cancer doesn’t grow back or spread. Kate: How long should I take hormonal treatments?Doctor: The number of years you should take hormonal cancer therapies normally depends on your age and cancer pathology. The average minimum recommendation for all hormonal cancer treatments, however, is five years on a daily basis often after or before another treatment is performed. Tamoxifen should be taken for 2-5 years for women who have been through menopause. If one of the treatments are no longer functional, another treatment is taken to complete the five years. For example, if someone is taking tamoxifen for 2 years but it suddenly stops working, they can use AI’s for 3 years to complete the 5 years. However, although it is not 100% confirmed yet, taking a treatment for more than 5 years may be more beneficial. Additionally, I have found that using a combination of treatments has greater benefits than just using one. For instance, I have found that taking tamoxifen for about 2-3 years followed by an AI for 5 years or vice versa, can have greater results. Other very helpful methods include taking AI for 5 years and taking tamoxifen for 6-10 years. Kate: How much does it cost?Doctor: The price of hormonal cancer treatments depend on the type of hormonal therapy, how often and long you have to receive it, and where you live. The drug treatments can be quite pricey though but I think we can find a way to negotiate a lower price especially as you are a minor. Kate: Which treatment do you recommend for me?Doctor: Because you are still quite young, I would recommend starting off with either tamoxifen or raloxifene. As the 5 or more years pass by though you can try getting luteinizing hormone releasing hormone (LHRH) analogs with AI’s instead. It’s all up to you but that is my recommendation. Kate: How do you know if hormone therapy is working?Doctor: It is extremely important that you are taking your assigned hormonal cancer treatment every single day or you may not receive the benefits. If you do so, your hormone therapy should be working. Otherwise, in order to 100% confirm, you will have checkups regularly for your cancer to make sure all is well. Kate: Who receives hormone therapy?Doctor: Hormone cancer therapy cannot be used for people with hormone receptor negative cancers because it would be completely useless and a waste of money and time! In fact, these hormone receptor negative cancers can’t respond to estrogen. Therefore, hormone therapy is used for people with hormone receptor positive breast, prostate, ovarian, or womb cancer. It is used sometimes as a backup plan for men with prostate cancer who can’t go through surgery or radiation therapy. Kate: What happens after my breast cancer is fully removed?Doctor: After your breast cancer is fully removed through whichever 5 year method you may choose, your breast cells are going to be retested. We will perform these tests again to make sure these cells are not cancer cells with receptors for estrogen and progesterone. Kate: Alright that’s all the questions I have for you today. Thank you so much! I will definitely be thinking about what treatment I want. Doctor: Yup! No problem. If you have any more questions feel free to give me a call or come visit my office.Kate: Okay thank you once again. I’ll see you later Dr. Kim.Doctor: See you, Kate!ReflectionQuestions answered: What did you learn that you found most interesting? What surprised you the most? What are you most interested in going forward in terms of further research into your area of study? What are some things completely new that you have learned? Do you think more in depth research should be conducted for this treatment? If so, why? My research was on hormonal cancer treatments. Going into this project, I did not think much about the treatment and did not know much about it either. However, when I learned that it was about breast cancer, I got pretty interested since this cancer is very sentimental and meaningful to me for numerous of reasons. One thing that I found to be the most interesting is that there are several different types of breast cancer. There is estrogen receptor positive, estrogen receptor negative, progesterone receptor positive, and progesterone receptor negative breast cancer. This was interesting to me because I never really knew much about breast cancer yet alone, how it is created. Additionally, I found the whole premenopausal and postmenopausal rules to be quite interesting. I never knew that going through this phase of menopause could be so effective and determining of the treatment one would get. It was actually quite amusing to see the effects of a hormonal inhibitor, such as an aromatase inhibitor, on a premenopausal woman versus the same hormonal inhibitor on a postmenopausal woman. The thing that surprised me the most was the ovarian suppression treatments. I found this to be surprising because I never knew you could potentially temporarily disable, or shut off, your ovaries preventing the production of ovaries. Besides almost everything, one new thing that really stuck out to me was the adrenal glands and estrogen in general. I found it to be so fascinating how after menopause, in which the ovaries shut off, naturally occurring estrogen is still able to be produced by these adrenal glands. In addition, the hormone estrogen also intrigued me because it’s so amazing how this hormone can do so much that can benefit us or even be used against us. For instance, it can strengthen our bones, lower our cholesterol, and provide us with a sense of well-being. However, it is also the main cause of breast cancer. In going forward in terms of further research into my area of study, I am eager and curious to find out how estrogen receptor negative and progesterone receptor negative cancers are perhaps treated. I also want to learn more about progesterone. Furthermore, I want to learn more about prostate cancer and hormones in males. I want to learn more about each specific treatment from the listed categories and how they affect both prostate and breast cancer in addition to womb and ovarian cancer. Most of my research about this treatment regarded estrogen. I want to know more about what progesterone is and more specifically how all of the hormonal cancer treatments affect them in comparison to estrogen. Yes, I believe that more in depth research and effort should be put in researching not only this treatment but other treatments as well. I believe that researchers should maybe find alternative cures and treatments for breast cancer and other hormone influenced cancers that have fewer side effects. Maybe they can find and create a cure that can only block out estrogen from the cancer cells specifically and not from other parts of the body that depend on the production of estrogen, such as our bones. I also hope that one day when the best and most effective cure is found for these cancers, the expensive price will decrease so that more people could afford these treatments and more lives could be saved.