Medical Oncology

Hormone Therapy
All breast cancers are now tested for estrogen receptor and progesterone receptor, which are molecules on the surface of cancer cells that can accept hormones and influence the growth of the cancer.  Breast cancers that are hormone receptor positive have two important characteristics.  First of all, they tend to be less aggressive than the same type of breast cancer that is hormone receptor negative. Also, they are influenced by various hormone manipulations that generally decrease the level of estrogen in the body. The percent of patients that have positive estrogen receptor increases with age. The response to various hormone manipulations is proportional to the level of estrogen receptor meaning that patients with high levels of estrogen receptor are more responsive to various hormone manipulations.

Various hormone manipulations are used in all aspects of breast cancer treatment including prevention, adjuvant therapy to prevent recurrence and in metastatic recurrent disease.

Prevention: There are a number of studies looking at tamoxifen in preventing breast cancer in patients with a high-risk based on family history or prior premalignant biopsies.  There are situations in which prevention has been shown to be helpful are in the premalignant conditions of ductal carcinoma in-situ and lobular carcinoma in-situ.  Several studies have shown that tamoxifen will decrease future breast cancer incidents by about 50% and ongoing trials with the aromatase inhibitors may show a higher prevention rate than tamoxifen.

Adjuvant Therapy: Patients with invasive breast cancer who are shown to be estrogen receptor positive and may be high-risk node negative or all node positive, benefit by additional antiestrogen therapy.  In premenopausal patients, the general therapy is five years of tamoxifen, but there are a number of research studies looking at more aggressive antiestrogen manipulation including LHRH agonist, followed by either tamoxifen or an aromatase inhibitor.  The results of these studies are pending, but should be available in the next year or two.  In postmenopausal patients, it has now been shown that the initial approach that yields the most benefit is to start with an aromatase inhibitor.  This clearly decreases the chance of recurrence and increases the long-term disease free survival.  Various research studies are now looking into whether more than five years of an aromatase inhibitor is beneficial and early indications are that 10 years of antiestrogen therapy in some situations may be more effective than five years.

Metastatic Disease: In those situations in which the breast cancer has recurred in distant sites and the tumor is estrogen receptor positive, hormone manipulation may control the tumor for many years.  Various hormone manipulations include tamoxifen in both premenopausal and postmenopausal women.  In postmenopausal women, the aromatase inhibitors and Faslodex also play an important role in tumor control.  If patients are responsive to these hormone therapies, other hormone approaches might include Faslodex or Megace or high dose estrogen.  In situations in which the tumor is hormone responsive, a sequence of hormone therapies can often keep the disease under control for many years before chemotherapy is needed.  The hormone therapy is much easier and often has longer response rates than chemotherapy.

Hormonal drugs that have been developed during the past 20 or 30 years include:

• Tamoxifen:  Tamoxifen is an estrogen receptor blocker that stops the uptake of estrogen in the tumor cell and places the tumor cell either in a resting state or causes the tumor cell to die.  Tamoxifen is effective in both premenopausal and postmenopausal patients.  The drug is generally well tolerated, but does have an increased incidence of uterine cancer and deep vein thrombosis, but these complications are rare and generally seen in patients over 65.
• The aromatase inhibitors including Arimidex, Femara, and Aromasin are oral medications that decrease the body’s production of estrogen in the ovaries, the adrenal glands, and in fat tissue.  These are used in a variety of situations in breast cancer, but only in postmenopausal women.  They are generally well tolerated, but do have some arthritis-like effects and in longer-term use are associated with some decrease in bone density.
• Faslodex:  Faslodex degrades the estrogen receptor and is also effective in postmenopausal women and is generally very well tolerated.  It is given as a monthly intramuscular injection.
• Oophorectomy:  Oophorectomy is the surgical process of removing the ovaries and is the oldest method of estrogen deprivation therapy.  In general, this has been replaced by the medications listed above, especially in premenopausal women, but is still being used in some specific situations.
• LHRH Agonists:  These are injections that stop the ovaries from producing estrogen and can be used in some situations in place of chemotherapy and can also be used to suppress the ovaries long term.

Chemotherapy
With earlier diagnosis of breast cancer many patients do not need chemotherapy because of their excellent prognosis. These  patients may need only local therapy, such as mastectomy or lumpectomy and radiotherapy or may need local therapy plus hormone therapy. In patients who need chemotherapy, that chemotherapy will clearly increase their disease-free survival and decrease their chance of recurrent metastatic disease.

The need for chemotherapy is based on multiple tumor and patient factors. These include age, menopausal status, nodal status, hormone receptors and the HER2-neu gene analysis of the tumor. Most node positive patients will benefit from the addition of chemotherapy and many higher risk node negative patients will also benefit from chemotherapy. Newer tests in node negative patients, such has the gene based Oncotype DX assay, help select which node negative patients may benefit from chemotherapy.  After all of these factors have been considered, some patients will have a great benefit with the addition of chemotherapy and some will have only a modest benefit.  At that point, discussion between the patient and the physician will help to determine what risk and toxicity the patient is willing to accept for what level of benefit. 

Most drug combinations in the adjuvant therapy of breast cancer include such drugs as Adriamycin, Cytoxan, Taxol, and Taxotere.  Newer trials are looking at the addition of biologic agents, such as Avastin, which decreases formation of blood vessels needed to sustain new tumor growth.  Newer concepts include addition of such drugs as Neupogen of Neulasta to be able to give the chemotherapy in a more compressed fashion with increased cure rates.  These chemotherapies in general over the past several years have become more aggressive and shorter in length and have less toxicity compared to older regimens.  This is because better antinausea drugs are available and drugs such as Neulasta are given to maintain normal blood count and thus greatly decrease the chance of infectious complications, which used to be a major problem with chemotherapy. In the special circumstance of tumors that overexpress the HER2-neu gene, the addition of Herceptin has greatly improved the cure rate in these more aggressive tumors. The HER2-neu gene is a growth regulatory gene that is overexpressed in about 20% of breast cancers. The addition of Herceptin in the adjuvant treatment of breast cancer has been one of the major advances in breast cancer therapy in the last five years.

Another concept in the chemotherapy of breast cancer at the time of diagnosis is the concept of neoadjuvant chemotherapy. This is a treatment regimen that involves giving chemotherapy prior to surgery thus converting patients who would otherwise need a mastectomy to breast conserving therapy with lumpectomy and radiation therapy.  The cure rates of chemotherapy given either before or after surgical treatment are the identical.

Metastatic Disease
Metastatic breast cancer is the situation in which breast cancer cells return in distant organs such as liver, lung or bone. Since metastatic breast cancer is generally not curable the goal of therapy is to prolong life with as little toxicity as possible. In patients whose tumors are hormone receptor positive, multiple hormonal modalities of therapy should be exhausted before proceeding to chemotherapy. There are a multitude of drugs that are used in metastatic breast cancer with the goal to prolong life with minimal toxicity as far as possible. Drugs that are used include Adriamycin, Cytoxan Taxol, Taxotere, Xeloda, Navelbine, Gemzar and Avastin. In patients whose tumor overexpress the HER2-neu gene, one can use Herceptin or the newer Anti-HER2 drug known as Tykerb, which is an oral agent.  Again the goal of these treatments is to improve survival and quality of life in patients with metastatic disease.

St. Joseph Hospital was participating in a number of national trials looking at various approaches to improving survival in metastatic breast cancer.