Chemotherapy means the treatment of cancer with drugs. In the case of breast cancer, drug treatment includes:
- Intravenous chemotherapy drugs. This is what people usually think of when they think of chemotherapy. It’ the stuff that makes your hair fall out. It is only given for invasive cancer. It is not given for DCIS.
- Endocrine therapy. This is a pill taken daily for 5 years or more. It can be used in patients with DCIs or invasive cancer.
As a general rule, patients with invasive cancer get either chemotherapy or endocrine therapy or both depending on 4 factors for the most part:
- Tumor markers
- Tumor size
- The presence or absence of cancer in the lymph nodes
- Gene expression prolife score (in certain cases)
There are 3 tumor markers:
- Estrogen receptors
- Progesterone receptors
- Her2 neu protein
When a breast biopsy shows cancer, special tests are done to determine whether or not there are receptors for the female hormone estrogen on the cancer cells. If 100 cells are tested and only one (1%) has an estrogen receptor (ER) and 99 do not (90%), the cancer is considered estrogen receptor positive (ER positive), although weakly positive. If, say 85% of the cancer cells are ER positive, the cancer is considered strongly ER positive.
As with estrogen receptors, breast cancer is also test for the presence or absence of progesterone receptors. There aren’t any drugs that specifically treat progesterone receptor positive (PR positive) cancersbut PR status is considered when classifying breast cancer subtypes.
Her2 is a protein, not a hormone. As with ER and PR, a special test called immunohistochemistry (IHC) is used to detect Her2. However, instead of there being 2 possible outcomes (positive or negative) as with ER and PR, Her2 has 3 possible outcomes: Her2 positive, Her2 negative or Her2 equivocal. When Her2 IHC is equivocal, a second test can be performed called fluorescence in situ hybridization (FISH). This can be the tie breaker. However, in a few cases, Her2 status by FISH is also be equivocal. In the case of two equivocal results, the patient is usually considered Her2 negative.
Breast Cancer Subtypes
Based on the ER, PR and Her2 status, breast cancer is classified into 4 subtypes.
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Chemotherapy Based On Cancer Subtypes
The following are general guidelines only. There are many other subtle considerations that go into treatment decisions.
- Her 2 positive tumors larger than 0.5 cm receive chemotherapy which includes Herceptin and possibly other anti Her2 drugs. If the tumor is also ER positive, endocrine therapy will be given after the chemotherapy and Herceptin are finished.
- Triple negative cancers regardless of size and lymph node status receive chemotherapy.
- All Luminal A and Luminal B tumors require endocrine therapy regardless of tumor size or lymph node status.
- Luminal A and B tumors that are smaller than 0.5 cm and have negative nodes do not need chemotherapy.
- Luminal A and B tumors that are greater than 5 cm and/or have 4 or more positive axillary lymph nodes shouldreceive chemotherapy in addition to endocrine therapy.
- Luminal A and B tumors between 0.6 and 5 cm and/or those with 1 to 3 positive axillary lymph nodes may or may not require chemotherapy. In this group of patients, a test called OncotypeDxcan be performed on the cancer tissue.
- Oncotype looks at the expression of 21 genes. Based on which genes are turned on and turned off, early stage, ER positive, Her2 negative cancers are classified into three categories.
Low risk for recurrence
This means that, based on the gene expression profile, if a woman takes endocrine therapy alone, it is unlikely the cancer is going to come back someplace else in her body. Furthermore, chemotherapy does not make the risk any better, so chemotherapy is not necessary.
High risk for recurrence
Based on the genes that are turned on and turned off, there is a significant chance breast cancer will recur someplace else in the body if the patient takes endocrine therapy alone. Adding chemotherapy will lower the risk of recurrent cancer.
Moderate risk for recurrence
This group is in the middle. There is a moderate chance of breast cancer appearing someplace other than the breast ifEndocrine therapy is taken. Adding chemotherapy will lower the risk but not as much as in the high-risk group. The benefit of chemotherapy has to be weighed against the risks of taking the drugs.
All patients, regardless of their Oncotype score, should be considered on an individual basis. However, this is especially true in the moderate risk group. Sometimes, patients with a moderate Oncotype score benefit fromTaxol and Cytoxan. This is a “mild” form of chemotherapy given once every 3 weeks for 4 cycles.
Patients with ER positive tumors (Luminal A and Luminal B) receive endocrine therapy.
The concept of endocrine therapy in ER positive patients is that if any cancer cells have escaped from the main tumor and are floating around in the body or if cancer wants to start growing someplace else in the breasts, they will starve to death because there is no estrogen to feed them.
Tamoxifen and the Aromatase Inhibitors (AIs) are prescribed once surgery and other treatments, such as chemotherapy and radiation are completed. The pill is taken once a day for 5 years. Sometimes this is extended to 10 years or more.
Tamoxifen and Aromatase inhibitors can be given before surgery in postmenopausal women with large, ER positive tumors (neoadjuvant endocrine therapy).
Tamoxifen blocks the effects of estrogen in the breast. It is given to pre menopausal women.
In women who have not had a hysterectomy, there is a one percent risk of uterine cancer with Tamoxifen. This can b e monitored with ultrasound. There is also a one percent chance of blood clots (deep vein thrombosis). Less serious side effects are hot flashes and bone loss.
Aromatase Inhibitors (AIs)
Aromatase Inhibitorslower the levels of estrogen in the blood.
AIs are more effective than Tamoxifen in postmenopausal women with ER positive cancer.
There Are Several AIs Including:
Side effects are less common with the AIs than Tamoxifen.
The AIs can cause heart problems and bone loss (osteoposis). Bone density tests can be used to monitor bone strength.
Combination chemotherapy is always used in breast cancer. This means giving at least two drugs that act on the cancer in different ways (mechanism of action). Several chemotherapy drugs have been shown to be effective in treating breast cancer.
Luminal A and Luminal B
ER positive, Her2 negative cancers with a moderate or high Oncotype score may receive a short course of chemotherapy with Cytoxan and Taxol. These drugs are given once every 3 weeks for 4 cycles (3 months of treatment) and start about a month after surgery.
Her2 positive patients often receive the same chemotherapy as triple negative patients but in addition to AC plus T, they also receiveHerceptin, which specifically targets the Her2 protein. Recently other anti-Her2 drugs have been developed and they are also very effective. Chemotherapy for Her2 positive patients can be given before surgery (neoadjuvant chemotherapy) or after surgery (adjuvant chemotherapy).
When given to patients with large tumors before surgery, the anti-her2 drugs result in shrinkage of the cancer in up to 80 percent of patients and complete disappearance of the cancer in 20 percent (complete pathological response).
One of the stronger drug combinations is Adriamycin and Cytoxan (AC). These two drugs are given every 2 or 3 weeks for 4 cycles.
Taxol or Taxotere (T), given once a week or every 3 weeks, often follows AC.
AC plus T represents 6 months of chemo and is a common regimen for patients with triple negative breast cancer.
If the patient has a large cancer, chemotherapy is often given first and is followed by surgery.
In many cases neoadjuvant chemotherapy shrinks the cancer.
A complete pathological response is associated with a very good prognosis.