Breast Cancer – Short Overview of the Main Treatments

Breast Cancer – Short Overview of the Main Treatments

Breast Cancer – Short Overview of the Main Treatments

Breast cancer, being the second most common cancer, has caused an epidemic around the world. While many of you are aware of this condition and know the traditional ways of detection and management, what do you know about the new developments in this field? There were many types of research, clinical trials and clinical studies conducted in the last few years to learn more about this disease. But, have we found that hope we are looking for?

What Do the Statistics Show?

Just being second to lung cancer, breast cancer affects more than 1.6 million women in the world, which makes up to 25% of all cancer cases that are recorded. According to the World Health Organization (WHO), about 508,000 people died around the world from breast cancer in 2011. Even though it was believed that this condition is a disease of the developed world, the statistics of GLOBOCAN 2008 changed this idea by showing that 50% of all breast cancers and 58% of all breast cancer deaths which were recorded, were from developing countries of the world. While the high incidence rates managed to somehow disseminate around the globe, the numbers vary according to the geographical regions. The incidence of breast cancer in the Western Europe is around 89.7 cases per 100,000 women while in eastern Africa it is about 19.3 per 100,000.  In the USA about 12% of women develop invasive breast cancer and the American Cancer Society predicts that the numbers will increase in 2017.

After publishing a study in 2002 that showed hormone therapy during the menopause increases the risk of this condition, the incidence of breast cancer decreased by about 7% in Hispanics as many women stopped using hormone therapy to control the symptoms of menopause. Also, since 1989, the breast cancer death rate has largely decreased as a result of increased awareness, successful cancer screening, and better treatments. Successfully, there are more than 2.8 million cancer survivors in the USA today. But, the question ‘whether we have a hope for breast cancer patients’, still remains the same.

Who Are at a Risk?

Starting from the information that is recorded in your genes to environmental and lifestyle factors, there are many risk factors for breast cancer. While being a woman and having BRCA1 or BRCA2 genes increases the risk of getting breast cancer, a history of other non-cancerous breast diseases or any breast conditions that can turn into cancer (carcinoma in situ) could also increase the risk in several folds. Other than that there are many other factors that may influence or cause this diseases and they are;

  • A family history of breast cancer: Having one of the first degree relatives with breast cancer can increase the risk.
  • Any dense tissues that are detected at a mammography.
  • Prolonged exposure of the breast tissues to estrogen that is produced within your body. This may occur in certain conditions such as;
    • Early puberty
    • Giving the first birth at an older age
    • Not giving birth to any children
    • Getting the menopause at a later age
  • Undergoing hormonal therapy with estrogen and progestin during menopause.
  • Undergoing radiation therapy
  • Being white
  • Alcohol consumption
  • Obesity
  • Older age

What Are the Traditional Methods of Diagnosing Breast Cancer?

Breast cancer gets diagnosed with a painless lump or a mass most of the time. Typically, this lump or mass is hard in consistency with irregular edges and it does not move well like the non-cancerous tumors. Anyhow, there are also breast cancers that are presented with a completely opposite picture. Hence, a tender, soft, rounded and a painful mass can also be a malignant tumor. That is why the most famous classic idea of only hard lumps being cancers have to be erased away and according to the new guidelines, a woman must consult a healthcare professional if she notices any difference of her breasts regardless of her age. Other than lumps or masses, there are many changes that might indicate signs of having breast cancer;

  • Breast swelling
  • Skin irritation or skin dimpling of the breast
  • Breast pain
  • Nipple pain
  • Nipple turning inward (retraction)
  • Redness of the nipples or breast
  • Skin thickening, hardening or scaling of the breast or nipple
  • Any kind of discharge from the nipples
  • Swollen lymph nodes in the armpit, and near the collar

Even though symptoms and signs of the breast are well known in diagnosing this condition, sometimes breast cancer can be detected just by the presence of lymph node enlargement. This is because, in certain cases, breast cancer can spread into the lymphatic tissues and lymph nodes, before the primary tumor in the breast becomes large enough to be recognized.

This disease of the breast is classified according to the size of the tumor, its spread and localization. This condition will also be staged according to these features. Anyhow, generally, there are two types of breast carcinoma and they are known as carcinoma in situ and invasive cancers. Carcinoma in situ is a pre-malignant condition, which will eventually turn into cancer and invasive cancers are malignant tumors that may grow and spread with time. The earlier the condition is diagnosed, the better the prognosis and survival will be. 

In order to confirm or exclude the diagnosis of breast cancer, a manual breast examination is done as the first step. Then, if there is any suspicion or abnormal findings, a screening procedure is assigned by a physician. The main breast cancer screening methods are mammography and ultrasound scanning of the breast. According to the new guidelines, all women who are above 40 years of age, should do a mammography every 2-3 years as a method of cancer screening. But, women under 35 years of age are not recommended to do mammography without any suspicious findings, as young breast tissue are highly sensitive to radiation exposure.

Ultrasonography (ultrasound) evaluates breast tissue structure and distinguish the form of abnormal tissues, for example, tumors from a cyst filled with fluid. If the results of a mammogram or ultrasound indicate the presence of any tumors in the breast, the doctor usually appoints the patient to have a biopsy test. A biopsy helps in determining whether the tumor is malignant, and if so, its type and stage. In addition, a biopsy material provides an answer to the question whether the tumor is hormone-dependent or not, which also may affect the treatment regimen. If necessary, for example, magnetic resonance imaging (MRI) and CT may also be carried out. After making the primary diagnosis, the doctor will determine the stage of cancer, for that, the details of the tumor size, its location, the presence of metastases and aggressiveness will be obtained. From this collected information the treatment and selection of optimal therapies are determined. 

The New Methods of Diagnosing Breast Cancer

Tests for circulating tumor cells (CTCs) is one of the new diagnostic methods introduced in the late years. As in other cancers, even in breast cancer, cells may break from the tumor and may travel in the blood circulation. Researchers have found that these cells can be detected with a sensitive lab test. The data from these tests help in predicting cancer returning but are not very effective in determining cancer survival. But, this test could be used to define the effectiveness of the treatment of advanced breast cancer.

Furthermore, according to another study, the presence of isotopes carbon-13 and nitrogen-15 in certain amounts in a tissue sample can reveal whether the tissue is healthy or cancerous. 

There are also newer imaging methods investigated and one of them is Scintimammography (molecular breast imaging). In this test, a mild radioactive drug known as a tracer is injected into a vein. This tracer attaches to the breast cancer cells and is then detected by a special camera. Anyhow, this method of breast cancer detection is still under investigations. Even though mammography may be helpful in finding suspicious areas of abnormal breast tissues, the specificity is still not satisfying enough. New studies are aimed at improving the technology so that breast cancer detection can be even done in specific situations such as in the dense breasts of younger women. Even though some studies have suggested that scintimammography can be as accurate as expensive magnetic resonance imaging (MRI) scan results, scintimammography should not be used as a replacement for screening mammograms at the moment.

What Are the Traditional Treatment Methods We Already Know?

There are many methods of treating breast cancer. As in all cancers, breast cancer can also be treated using traditional methods of treatment such as surgery, radiotherapy, and chemotherapy. But, additionally, hormonal therapy is also used as the main method of treatment in breast cancer.

The method of surgical approach, the extent of surgical removal of breast tissues and surrounding tissues and the methods of breast reconstruction approach, depend on the severity and the type of the breast cancer. Also, the dose of radiation and chemotherapy, the source of radiation and the medication used in chemotherapy is determined according to the condition. 

During hormone therapy (one category of treatment apart from usual ones), the doctors usually check for the hormone sensitivity of the tumor. According to the results of investigations, the tumors will be classified as;

  • Estrogen receptor positive breast cancer
  • Progesterone receptor positive breast cancer

Using hormonal therapy will reduce the size of the malignant tumor and its spread. Even though some oncologists use invasive methods such as surgical removal of ovaries as a part of hormonal treatment, there are also medications that could block, deactivate or destruct the hormone sensitive receptors of the tumor;

  • Selective estrogen receptor modulators (SERM)
    • These medications block estrogen from attaching to its receptors in the tumor cells and thereby slow its growth and kill its cells. The drugs that belong to this category are; Tamoxifen, Toremifene (Fareston), raloxifene (Evista).
  • Aromatase inhibitors
    • These are postmenopausal medications, which block the production of estrogen after the menopause by blocking the enzyme that converts androgens to estrogens. It includes exemestane (Aromasin), anastrozole (Arimidex) and Letrozole (Femara).
  • Fulvestrant (faslodex)
    • This is a medication that is used in postmenopausal women and it blocks the estrogen receptors on the tumor cells and signals the cells to destroy them. 

Biological Therapy (Targeted Therapy Second Category) – New Developments of Breast Cancer Management Medications

Biological therapy includes targeted and specific drugs instead of general drugs that were earlier used. With these medications, the treatment has shown to be more effective and the generalized damage to the healthy cells and tissues is minimized. The drugs that used in targeted therapy are;

  • Trastuzumab (Herceptin)

    • This medication blocks the human epidermal growth factor receptor 2 (HER2) and thereby reduce the growth and cause the cells to die.
  • Pertuzumab (Perjeta)

    • This is used in metastatic breast cancer together with Trastuzumab to accompany chemotherapy. It is used in women who have not received any other drug treatments earlier.
  • Ado-trastuzumab (Kadcyla)

    • This is a combination of drugs which includes Trastuzumab together with a cell-killing drug. Trastuzumab finds the cancer cells and then the cell-killing drug is released to kill them. This is a good option for women with breast cancer metastasis.
  • Lapatinib (Tykerb)

    • This is also a drug associated with the HER2 receptor and is used in advanced cancer together with chemotherapy or hormone therapy.
  • Palbociclib (Ibrance)

    • Palbociclib is used together with aromatase inhibitors with hormone receptor-positive breast cancer.
  • Everolimus (Afinitor)

    • It's used in in women with advanced breast cancer in combination with exemestane, which is an aromatase inhibitor. 

What Are the Other Medications That Are Under Research, to Be Used for Prevention and Treatment of Breast Cancer? 

While researchers still continue to look for medications that prevent breast cancer in women who are at a high risk, there are some medications such as Tamoxifen and Raloxifene that have been already approved to be used to treat and prevent breast cancer.

Also, there are many ongoing clinical studies trying to find out unintended breast cancer reduction of already known drugs.

Fenretinide – A vitamin A derivative. In a small clinical study, it showed to reduce the risk of breast cancer as effectively as tamoxifen.

Statins (Atorvastatin, Lovastatin) – These drugs are usually used to reduce high cholesterol levels, but, the researchers believe they might be effective in treating and preventing breast cancer.

Certain dietary supplements such as grape seed extract, folate, omega 3, vitamin B6 and B12, hydroxytyrosol and curcumin are also under investigations.

Poly ADP-ribose polymerase (PARP) inhibitors are still being studied. When they were used in certain clinical trials to see if they can be used in the treatment of breast cancer, certain types of breast cancers showed promising results. It was shown that this drug is useful in treating breast cancer caused by BRCA gene mutations. But, more studies and clinical trials need to be conducted further before their actions are completely understood.

The next on the list is anti-angiogenesis drugs. Angiogenesis is a process where new small blood vessels and connections are grown. In cancer tumors, the blood supply is a very important part as these growing tumors grow new vessels around them to nourish them so that they may grow well. If the blood supply of a tumor is disturbed the tumor growth and spread can be controlled. Anyhow, bevacizumab (Avastin), an anti-angiogenesis drug was under clinical studies and did not show promising results, anti- angiogenesis drugs are still considered to be an effective approach in breast cancer management. Therefore, several other drugs are being tested in clinical trials.

Bisphosphonates are medications that are usually used to treat osteoporosis but are now under clinical trials to see its affectivity in treating breast cancer. Certain drugs such as pamidronate (Aredia) and zoledronic acid (Zometa) are used to strengthen the bones that are affected by metastatic cancer lesions. Also, another clinical trial showed that zoledronic strengthens the effects of hormone therapy and chemotherapy. The patients who received zoledronic together with chemotherapy showed a greater tumor size reduction than the patients who received only chemotherapy. Also, it was shown that combining zoledronic together with chemotherapy or radiotherapy reduces the risk of cancer coming back.

Denosumab (Xgeva) is also used to strengthen the bones that are affected by metastatic cancer lesions.

Abraxane is an Albumin-Bound Nanoparticle Drugs and is known as nanoparticle albumin–bound paclitaxel.  It was released recently as a new chemotherapy drug for breast cancer. This is actually not a new drug, but a new version of administering an old drug. When Abraxane is administered as a chemotherapy drug, there is no need of giving any premedication and thereby, the related side effects can be ignored. Also, this drug reduces the infusion time of the chemotherapeutic drug.

Herceptin (trastuzumab) was lately approved for the treatment of early-stage of breast cancer that is HER2 positive. According to a study released last June more than half of women who received Herceptin as a part of chemotherapy during presurgical interventions had their tumors completely disappeared? The results were so promising that the researchers stopped the trial early and are now in use for breast cancer treatment.

Also, a study conducted by the cancer research institute in London showed that the combination of trastuzumab (Herceptin) and lapatinib (Tyverb) significantly obliterated all the signs of breast cancer in 11% of people within 11 days. The patients who received this drug combo did not need any chemotherapy as well. 

What Are the New Surgical Interventions Developed in Treating Breast Cancer?

There are various types of surgical interventions available including breast-conserving surgery, mastectomy, and oncoplastic surgery. The option of breast conserving surgery can be for women with early stages of breast cancer, but it can cause disproportionate breast size and shape. The larger size tumors obviously need a radical approach with mastectomy. On the other hand, there are doctors who conjoin cancer surgery with plastic surgery and perform necessary reconstruction during the initial surgery. If needed, further surgery to modify the other breast in order to match with the operated breast.

What Is Virotherapy and How It Can Be Used in Breast Cancer?

Virotherapy is one of the newest fields of medicine which use the viruses as a method of killing the cells of cancer tumors. Therefore the viruses are known as oncolytic viruses and these viruses eliminate cancer cells by invading into malignant tumors. Most viruses that we know show a high tropism for cancer cells. Therefore, the scientists thought that they can be used in treating cancers. As these viruses invade normal body cells and cause damage, the same theory was used by the scientists and they made oncolytic viruses out of those viruses we already know. After many studies, they found out that their theory was practically implementable and these special viruses killed cancer cells very effectively.

At the moment Oncolytic virotherapy is carried out using only one approved medication known as “Rigvir” and it is a genetically non-modified collection of viruses.

There are many more clinical studies that have not been published yet and also many more pending clinical trials. Anyhow, what we already have discovered is precious when it comes to successful detections and treatment. In the last few years, some drugs that are mentioned above increased the motivation and strengthened the hope of finding a cure for breast cancer. Even though we are not yet there, we should realize that we have come a long way and the zeal is not so far! 

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Last update 08/10/2019

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