HORMONAL OR ENDOCRINE THERAPY

If your cancer was tested and found to be estrogen and progesterone positive, that means  its growth was dependent upon the naturally occurring estrogen and progesterone in your body. The main source of these hormones is in the ovaries. However, post menopause, estrogen is converted by androgen and can still “feed” a breast cancer cell.

The advent of endocrine therapy has changed the face of breast cancer dramatically. In premenopausal women drugs such as Tamoxifen and Evista  block the estrogen receptors at the cellular level so cancer is not able to grow.

Removing a woman’s ovaries has also shown to be a great benefit. One of the discoveries  that doctors have made is that the chemotherapy induced menopause is the true benefit of chemotherapy in estrogen/progesterone positive women, because the hormones have been shut down by the chemotherapy drugs. Without the hormones in the body, the cancer cannot grow. A chemically induced menopause  can be achieved by drugs such as Lupron and Zoladex.

In post-menopausal women, the use of aromatase inhibitors like Arimidex, Femera and Aromasin, naturally occurring androgens that convert to estrogen, are stopped. These  drugs block the  aromatase enzymes which make this happen and as a result prevent cancer growth.  

The following is a list of endocrine therapy drugs.  

Aromatase inhibitors for post menopausal women only:

Femara

Arimidex

Aromasin

Premenopausal  and post menopausal women can take:

Tamoxifen

Evista

Faslodex

Note: The STAR Trial, part of the The NSABP Study of Tamoxifen and Raloxifene, concluded that when directly comparing  Evista to Tamoxifen, Evista is as effective as Tamoxifen in reducing the risk of invasive breast cancer, but may be less effective in reducing the risk of noninvasive breast cancers such as ductal carcinoma in situ (DCIS). Evista  has less risk of blood clots than Tamoxifen, except in women with coronary artery disease or who are at risk of coronary artery disease. These women should not take Evista because it has been found to increase the risk of blood clots and fatal strokes.

Faslodex was the first estrogen receptor antagonist with its use,  estrogen is no longer able stimulate cellular growth. The Food and Drug Administration (FDA) has approved Faslodex for hormone treatment in postmenopausal women who have failed other endocrine therapies.

Side Effects of Endocrine Therapy

Tamoxifen:

Hot flashes, irregular menstrual periods and vaginal discharge or bleeding. There is a small increase in developing blood clots. Tamoxifen increases a woman’s risk of developing uterine cancer.  The same risk women taking hormone replacement therapy face.

RISK VS BENEFIT: Uterine cancer can be detected at an early stage and treated quite successfully. The benefit of Tamoxifen in preventing breast cancer outweighs the slight risk of  developing uterine cancer.

HOWEVER: All women  taking anti-estrogen therapy should go for regular gynecologic examinations.

Aromatase inhibitors:

 Joint pain and  decreased bone density

Women who took Tamoxifen for 2 – 3 years and then switched to Aromasin showed a marked improved survival. However, they also  showed a minor loss of bone density. After almost five years of follow-up, bone fractures had occurred in 7% of women who switched to Aromasin and 5% of women who remained on Tamoxifen.

RISK VS BENEFIT: Women survive longer on aromatase inhibitors and their five year  bone fractures rate is 7%. If they remain on Tamoxifen, their survival is shorter and their bone fracture rate is 5%.

The benefit of switching to an aromatase inhibitor outweighs the risk of remaining on Tamoxifen

Who benefits from Endocrine Therapy?

The use of hormonal therapy appears to benefit all women with hormone receptor-positive early-stage breast cancer. It significantly reduces the risk of cancer recurrence.

In women with ductal carcinoma in situ (DCIS) research has shown that the use of  Tamoxifen after surgery and radiation was more effective for preventing breast cancer recurrence in patients with DCIS than surgery and radiotherapy alone.

Women with metastatic breast cancer benefit from initial treatment with hormonal therapy. Should it recur, metastatic women benefit from switching to a different endocrine therapy.

It can be used in the following ways: to treat newly diagnosed metastatic disease; to treat metastatic disease that once was treated with Tamoxifen; to treat metastatic disease that was once treated with another aromatase inhibitor.

NOTE:  A clinical trial  directly compared Femara and Tamoxifen as initial hormonal therapy in postmenopausal women with metastatic breast cancer. The results of the trial showed that Femara is superior to Tamoxifen.

BENEFITS OF ENDOCRINE THERAPY

Tamoxifen may help to lower blood cholesterol and reduce the rate of bone loss (osteoporosis). Two clinical studies have reported that women treated with Tamoxifen had a lower risk of cardiac disease than women not treated with Tamoxifen. Evista is FDA-approved for the prevention and treatment of osteoporosis.

Recent study findings

Aromasin  and Faslodex  are approved for treatment of women with metastatic breast cancer that has stopped responding to Tamoxifen.

Aromasin: Research indicates that Aromasin appears to be superior to Tamoxifen. In a recent study, women treated with Aromasin had nearly 3 times more anti-cancer responses than those treated with Tamoxifen (41% versus 17%).

Faslodex: Faslodex appears to be an  effective first-line endocrine therapy. Research indicates that Faslodex was superior to Tamoxifen , 44% versus 30%, respectively

Conclusion:

Being diagnosed with estrogen and progesterone positive cancer has its benefits. Women are living longer because of the many weapons in their arsenal post treatment. The use of endocrine therapy has changed the landscape of breast cancer survival… in OUR favor.

ABOUT THE SIDE EFFECTS....

Many women have no trouble at all with any of these therapies. However some do and to such an extent that they stop treatment. This is a very worrisome thing to many oncologists. Since women are on the "honor system" because they take these drugs at home, it is hard for their doctors to monitor their care.  One of the reasons that women are surviving breast cancer longer is because of the advent of these drugs. So everything must be done to manage the side effects and remain on course.

For increased hot flashes, there are drugs like Effexor, an anti-depressant, that can help decrease their frequency. For the joint pain and stiffness, it has been found that women who are found to be vitamin D deficient experience more pain than women who have blood values of vitamin D above 45. Get your vitamin D level tested and then correct it if you are deficient. Not only can it reduce joint pain, it may help prevent breast cancer recurrence.

Bone loss is another concern. New studies have shown that taking bisphosphonates, bone density drugs such as Zometa, can prevent bone loss and it can also help prevent cancer spreading to the bones.

Please refer to these Resources

Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM. Endometrial cancer in Nolvadex®-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. Journal of the National Cancer Institute 1994;86:527-537.

Coombes RC, Paridaens R, Jassem J et al. First Mature Analysis of the Intergroup Exemestane Study: a Randomized Trial in Disease-free, Postmenopausal Patients with Early Breast Cancer Randomized to Continue Tamoxifen or to Switch to Exemestane Following an Initial 2-3 Years of Adjuvant Tamoxifen. Presented at the 2006 ASCO Annual Meeting. Abstract #LBA527.

Howell A, Cuzick J, Baum M et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) Trial after Completion of 5 Years’ Adjuvant Treatment for Breast Cancer. The Lancet. 2005;365:60-2.