Imagine being asked to train for the battle of your life and at the very same time learning a completely new and foreign language. Well that is exactly what happens to women newly diagnosed with breast cancer. Not only must you confront the scariest word in the world (cancer) and your own fears but in order to understand what is going on you must learn how cancer doctors think and what they are saying. An understanding of the “how and why” cancer doctors think can really help you and your family make the most out of consultations and 2nd opinions. This article will give the general outline of how a medical oncologist views treating early breast cancer (EBC) for cure. EBC, for this article, includes what we call stages I, II, and III and means that the cancer has not spread to other organs of the body.
In order to cure EBC we must understand and accomplish two goals: Local control and Systemic control. Local control in EBC is to remove or destroy “local disease” and prevent local recurrence in the breast by performing surgery or radiation on the breast and, where appropriate, the axillary (arm pit) lymph nodes. Patients with breast cancer that has not spread visibly outside the breast may be cured by such local treatment alone. Systemic control is using combinations of chemotherapy, endocrine therapy, or targeted therapy as an adjuvant (“Adjuvant Therapy”) to surgery in patients with EBC. Adjuvant therapy is used to eliminate or to prevent the growth of distant microscopic metastases, and in so doing will improve overall survival and create more cures than local control would if used alone. By combining the best proven local control with the best systemic therapies we achieve the overall highest cure rates.
For local control, the generalized treatment approach for most women with EBC is breast conserving surgery, dissection of the axillary lymph nodes (or sentinel lymph node biopsy), followed by radiation therapy. However, in some cases a modified radical mastectomy (removal of the breast and axillary lymph nodes) may be necessary, with or without radiation therapy.
For systemic control and the choice of adjuvant therapies (chemo, hormones, and targeted therapy) the doctor must know a few key details about the biology of the breast cancer. The short list of important details includes:
• Size of cancer in the breast
• Presence and number of lymph nodes with cancer
• Presence or absence of the female hormone receptors (estrogen & progesterone)
• Presence or absence of a key protein known as “Her2”
With these details an oncologist can make accurate predictions about microscopic breast cancer cells in the body. This allows us to discuss the likelihood of cure or recurrence of breast cancer after surgery and thus determine the best recipe for systemic therapy for any patient.
Local Control – Surgery, Radiation, or Both
Types of breast surgery
The type and extent of breast surgery to be selected is dependent upon the size and stage of the tumor. The major breast cancer treatment options are:
• Mastectomy, with or without breast reconstruction
• Breast conserving procedures such as wide local excision, quadrantectomy or lumpectomy
• Axillary lymph node dissection, to determine staging and for treatment planning
The form of mastectomy generally adopted is known as modified radical mastectomy or simple mastectomy, a technique that involves total removal of the breast and surgical dissection of the armpit, whilst preserving the chest muscles.
Currently, breast-conserving procedures are now increasingly employed and regarded as the treatment of choice for breast cancer. For patients with tumors up to 5 cm, wide local excision or lumpectomy can be performed and with dissection of the axillary lymph nodes, these procedures can offer identical results to radical surgery. In some countries, quadrantectomy, with or without supplementary irradiation, is a frequently used form of breast-conserving therapy.
The aim of these breast-conserving procedures is to remove a margin of normal tissue surrounding the tumor itself. If positive margins are discovered on histological examination of the excised tissue, the surgeon can remove additional tissue with a re-excision.
Radiation therapy involves the use of ionizing radiation to damage actively dividing cells. Since cancerous cells are dividing more rapidly than most healthy tissues, cancerous cells tend to be killed first; however, the treatment is not specific. Radiation therapy can be used as primary therapy in cases of inoperable (usually stage III) disease or when the patient refuses or is unsuitable for surgery.
External beam radiation is the type of radiation therapy usually employed in breast cancer. The radiation is focused from a source outside the body onto the area affected with cancer. Patients are usually treated five days per week in an out-patient setting, with a carefully pre-calculated dose being given over a period of about 6 weeks.
In early breast cancer, radiation therapy is most-commonly used as adjuvant treatment, i.e. postoperatively. Postoperative radiation therapy greatly reduces the frequency of local recurrence, particularly in patients with axillary node- positive disease. It is used following simple mastectomy and partial axillary node excision and also following more breast-conserving lumpectomy or wide local excision.
Systemic Control – Adjuvant Therapy
Hormone therapy, also known as endocrine therapy, has become a major mode of treatment for all stages of breast cancer. The majority of breast cancers are of the type in which growth is stimulated by the female sex hormones, estrogen and progesterone.
The principles for this type of treatment are based on starving the cancer of the hormone-induced growth stimulus and the current forms of endocrine treatment include:
• Blocking the Estrogen receptor with a selective estrogen receptor modulator (tamoxifen) or an estrogen receptor antagonist (fulvestrant)
• Suppressing Estrogen synthesis, in postmenopausal women, with an aromatase inhibitor (anastrozole, letrozole, exemestane)
• Ovarian ablation, by surgery or radiation therapy or medically by administration of a luteinizing hormone-releasing hormone analogue (goserelin) in premenopausal women.
The first step in establishing the suitability of a patient for endocrine therapy is to determine the hormone sensitivity of the tumor or its receptor status. Tumors with high levels of the receptor proteins are described as estrogen receptor- positive (ER +) and/or progesterone receptor-positive (PR +). Tumors not expressing significant amounts of either of these receptor proteins are described as receptor-negative and are unlikely to respond to endocrine therapy.
The medical means by which removal of the hormone is achieved depends primarily on the menopausal status of the patient, as the source of estrogens before and after the menopause is different. Ovarian ablation is a suitable treatment for premenopausal women, but is of no value to postmenopausal patients. In contrast, blocking of estrogen by the use of an aromatase inhibitor is an effective treatment for postmenopausal women but alone is of little or no value to premenopausal patients.
Chemotherapy drugs work by interfering with the ability of cancer cells to divide. Nearly all chemotherapy treatment recipes used in breast cancer involve two or more agents used together. Combination chemotherapy exploits the fact that different drugs act in different ways; and studies have shown that two or more drugs used together increase the chances of killing more cells. Chemotherapy has become established as one of the major therapeutic modalities in breast cancer.
Chemotherapy is administered in a series of cycles with rests in between successive cycles to help minimize side effects as well as to allow time for cells in the patient’s normal tissues to recover. The number of cycles varies depending on the agents used; typically four to eight cycles are employed within a course of chemotherapy.
There are several different types of chemo drugs used to treat breast cancer. The main ones are anthracyclines, alkylating agents, and taxanes. Most, if not all, chemotherapy drugs target dividing cells at the point in the cell cycle when DNA is copied or the cell is dividing into daughter cells.
In early breast cancer, chemotherapy is most usually applied as adjuvant treatment following excision of the tumor, with the aim of killing any circulating microscopic tumor cells that have spread. These are cells that we know exist (based on size, lymph nodes, etc) but we cannot see despite the most advanced scans and x-rays.
Adjuvant chemotherapy is the systemic treatment of choice in lymph node- positive patients with ER-negative tumors, irrespective of menopausal status, and is considered as an option in addition to endocrine therapy in patients with ER-positive tumors. Previously, lymph node-negative patients were not considered for chemotherapy as it was widely believed that the disease was confined entirely to the breast and, therefore, would most likely be cured by local treatment. However, several large clinical trials showed significant improvements in survival in these patients when they receive adjuvant chemotherapy.
Overall, studies have shown that adjuvant chemotherapy significantly alters the natural history of breast cancer in almost all patients, improving survival and creating more cures.
Targeted Therapy (trastuzumab)
Recently, a new molecularly targeted therapy has joined the adjuvant therapy program for EBC. Trastuzumab is a “humanized” monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2). After attaching to the HER2 protein on the breast cancer cell surface, trastuzumab induces cell death. Trastuzumab has been known to help women with metastatic breast cancer live longer and better for many years. This medicine is only effective if the breast cancer has too many copies of this protein (over expression) inside the cancer cell. Only recently has it been shown that by adding 6 to 12 months of treatment after surgery could result in even higher long term disease control rates for EBC. Again all of this translates into more cures in the setting of EBC.
In summary, the more you know about breast cancer and the more you know about how your doctor thinks will help you make the most of your time in a doctors office. Beating breast cancer takes a team approach and no one doctor can do it all. The key is education and finding a doctor who can coordinate all of your needs to bring you (and your family) a cure today.
[Image source: Wikimedia Commons]