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cancer

Breast Cancer: Where we’ve been and where we’re going
Breast Cancer: Where we’ve been and where we’re going In the past, a surgical procedure known as a radical mastectomy was utilized to attempt to remove the entire cancer, in addition to ample amounts of normal surrounding tissue. Later, after investigations proved that most women did not require such aggressive treatment to control the disease locally, a form of surgery known as breast conservation, in effect, a lumpectomy, replaced the mastectomy in most settings.

Over the years, there have been several innovations and improvements in the treatment and management of breast cancer. All disciplines of cancer therapy, including surgery, radiation therapy and systemic therapy, the latter in the form of chemotherapy, biologic therapy, and hormonal therapy, have been utilized to improve the outcome in women diagnosed with breast cancer. This article outlines how we have changed our approach to dealing with breast cancer over the years and where that has brought us in determining what our future interventions will likely be.

Some newer radiation therapy techniques are being investigated. One is reducing the number of radiation treatments as each dose of radiation is increased. This technique has been studied in Europe and is known as hypo-fractionated radiation. Another is actually changing the radiation source altogether and using radiation “implants” known as brachiotherapy. A small source or “seed” of radiation is inserted into the breast tissue for a very short period of time; and in approximately one-week’s time, the radiation can be delivered. This procedure is still experimental and most often used in older women with very low-grade tumors.
Most are aware that the surgical approach to breast cancer has changed dramatically over the past few decades. In the past, a surgical procedure known as a radical mastectomy was utilized to attempt to remove the entire cancer, in addition to ample amounts of normal surrounding tissue. Later, after investigations proved that most women did not require such aggressive treatment to control the disease locally, a form of surgery known as breast conservation, in effect, a lumpectomy, replaced the mastectomy in most settings. The reason for this was that the main concern is to keep breast cancer from recurring in distant sites, or metastasizing, as opposed to focusing solely on local recurrence. One of the essential components of being able to utilize breast conservation, or a lumpectomy, is additional localized therapy in the form of radiation. Radiation has typically been given to women by an external source, known as a linear accelerator over a five to six week period. This is still the most frequently used option following a lumpectomy.


Lately, there has been a new medication known as PARP inhibitors. This enzyme is responsible for repairing DNA damage in cancer cells in order for cancer to survive.
Changes in management of cancer
The area that has seen the most change in breast cancer management has been that of systemic therapy which refers to treating the entire body system. It is referred to as systemic therapy as opposed to chemotherapy because for several years we have had an alternative to chemotherapy in treating breast cancer that has spread, or metastasized. This treatment is commonly referred to as hormonal therapy. Hormonal therapy was first applied in breast cancer. Breast cancer cells in many women depend on female hormones, known as estrogen and progesterone, to survive. Blocking or depriving these hormones has been found to be effective when the cancer has spread or metastasized in addition to preventing the cancer from returning after surgery. The latter approach is known as adjuvant therapy. For several years, the main hormonal therapy medication utilized was a drug known as tamoxifen. Tamoxifen basically competes with estrogen for activity in affecting the cancer cells. There are now three commercially available hormone-affecting medications for use in post-menopausal females to prevent recurrence and to treat advanced breast cancer. It is important that women understand that they have to be confirmed as post-menopausal for a significant period in order to take these medications or they will not be effective in preventing the recurrence of breast cancer. The reason is that these medications, known as aromatase inhibitors, work by blocking estrogen production from the adrenal gland tissue which is the only tissue in post-menopausal females producing estrogens. They do not work if estrogens are being produced from the ovaries; therefore, pre-menopausal females can rely only on tamoxifen.


Chemotherapy has been used to both treat advanced breast cancer and as an adjuvant therapy. For several years, chemotherapy was the only approach that could be utilized to prevent recurrence of breast cancer in women with non-hormone “feeding” tumors.
The other form of systemic therapy for breast cancer has been in the form of chemotherapy and biologic therapy. Chemotherapy has been used to both treat advanced breast cancer and as an adjuvant therapy. For several years, chemotherapy was the only approach that could be utilized to prevent recurrence of breast cancer in women with non-hormone “feeding” tumors, i.e. cancers that could not be prevented with the use of medications like tamoxifen or aromatase inhibitors. In addition, once breast cancer had spread to other organs and could not be treated with hormonal therapy, chemotherapy was the patient’s only option in these non-hormone “feeding” tumors.

Another systemic approach to breast cancer has been “biologic” or what has also been referred to as “targeted” therapy. This form of therapy could be considered similar to hormonal therapy in that it is destroying breast cancer cells or preventing them from growing by non-chemotherapy methods, in other words, trying to block the growth of tumor through biologic growth pathways. These forms of therapy are not considered “cytoxic” and therefore do not have the same side effects as chemotherapy does. They still have a considerable number of side effects; however, often affecting the GI tract, and the skin, as opposed to blood cell counts. This therapy is also more discriminate in destroying cancer cells as opposed to normal body cells. In addition to trastuzumab and lapatinib, a medication known as bevacizumab (Avastin®) has been added to chemotherapy to make it more effective against breast cancer. Bevacizumab has been used in other malignancies such as colorectal and lung cancer to increase the effectiveness of chemotherapy. Bevacizumab is known as a vascular endothelial growth factor receptor inhibitor or VEGF- inhibitor and it is not completely clear why it enhances the effectiveness of chemotherapy. It was initially believed that it might have some ability to enhance the delivery of chemotherapy to tumor cells and possibly later on, after more extended use, decrease the blood supply to developing cancer cells in the body.

More recent developments
More recent developments in breast cancer therapy have focused on the opinion that breast cancer can be divided into three types.
First are the hormone responsive cancers that are typically slow growing, seen in older women, and can be treated effectively without any chemotherapy using hormonal agents as previously expressed.
Second are the HER-2 over-expressing cancers that used to be considered very aggressive that now with blocking HER-2, are considered to have a much better prognosis.
The third form is known as “triple negative” cancers that have neither estrogen nor progesterone receptors in addition to no HER-2 over expressive features. These breast cancers are now considered as having the worst prognosis and the only option is chemotherapy, with possibly the addition of bevacizumab, in preventing these tumors from recurring after surgery or progressing once they have spread outside the breast and are advanced.

Within the last decade, there has been a major revelation in understanding certain types of breast cancer. One has been the expression of a marker or receptor known as HER-2. In the past, this feature was thought to be associated with a very aggressive form of breast cancer that had an extremely poor prognosis even when caught at early stages. With the advent of medications that block HER-2 such as trastuzumab (Herceptin®) and more recently, lapatinib (Tykerb®), a very bad form of breast cancer has achieved a much better prognosis. Blocking HER-2 has not only been applied in metastatic disease, but has now been found to be effective in preventing HER-2 over-expressive breast cancers from recurring after surgery.
New Medications
Lately, there has been a new medication known as PARP inhibitors. PARP is an abbreviation for Poly (ADP-Ribose) Polymerase (PARP). This enzyme is responsible for repairing DNA damage in cancer cells in order for cancer to survive. It has been found that in some triple negative tumors, medications that inhibit this PARP have been effective in increasing the response rate to chemotherapy. As one can imagine, if you interfere with a repair mechanism in a cancer cell and in addition to that, add a medication such as chemotherapy that induces DNA damage, you will increase the effectiveness of the chemotherapy.

Recently discovered is a new approach to destroying cancer cells that combines both the previous cytotoxic chemotherapy with the new-targeted therapies. One is a medication known as trastuzumab/DM- 1. This is sort of a “Trojan horse” approach to destroying cancer cells. In this case, tumor cells that over express HER-2 will, in addition to binding the drug that is similar to trastuzumab, be destroyed more selectively by a potent chemotherapy drug known as DM1 that is attached to trastuzumab. Basically, it directs the chemotherapy to the cancer cells as opposed to allowing the chemotherapy to simply circulate throughout the body and cause toxic effects on both the normal and the cancer cells.

Management of breast cancer has gone through some major changes over the past century and will continue at an accelerated pace in the future.

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"Breast Cancer: Where we’ve been and where we’re going"
   authored by:
ONCOLOGY
Dr. Fleming earned his MD degree from the University of Louisville, Kentucky, and completed his fellowship at the University of Kentucky which included an externship at the National Cancer Institute.He became a tenured professor in hematology/oncolog...



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