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Treatment of Metastatic/Advanced Breast Cancer

General

The introduction of modern systemic treatment appears to increase survival in patients with metastatic disease. Many patients can benefit from multiple treatment options. The treatment course for each individual patient, depends on both tumor characteristics, the effect of each treatment, toxicity, and the patient’s general condition. An oncologist (or specialist with broad medical oncology competence) should be responsible for all cytostatic treatment and all sequential endocrine treatment of advanced breast cancer disease.

For potentially endocrine-sensitive metastatic disease, endocrine treatment is primarily chosen before chemotherapy. Despite chemotherapy may give a higher response rate, there is no survival benefit by starting chemotherapy before endocrine treatment. Also, endocrine treatment causes less side effects. The choice of treatment strategy should primarily be based on: to what degree the disease appears to be endocrine sensitive, extent of the disease (especially visceral), and how quickly the disease progresses (aggressiveness). Patients with rapid progression should be given chemotherapy initially. In most instances this applies to patients with liver involvement and patients with dyspnea from lung carcinomatosis.

The antiestrogen tamoxifen was previously the initial treatment choice for hormone receptor positive metastatic disease because of its efficacy and low toxicity. This changed after the introduction of specific aromatase inhibitors. Anti-aromatase drugs (non-steroidal or steroidal) are now considered to be the first treatment choice in postmenopausal women whether they have previously used adjuvant tamoxifen or not. Of new medications, the antiestrogen fulvestrant has shown efficacy for metastatic breast cancer, also subsequent to use of aromatase inhibitors. Megestrol acetate was used routinely after progression on tamoxifen before aromatase inhibitors were introduced. Today, megestrol acetate is sometimes used after treatment with the above mentioned drugs. There are multiple studies showing effect of using steroidal aromatase inhibitors (exemestane) after non-steroidal (letrozole, anastrozole) while there is less documentation for use of non-steroidal after steroidal. There are also studies showing efficacy of estrogen therapy.

Everolimus in combination with exesmestane is a possible choise after progression on letrozole/anastrozole, usually for 2. or 3. line. Everolimus in combination with tamoxifen may be an alternative when eksmestan has previously been given (applied for through paragraph 3 a).

The two most effective single groups of cystostatic drugs for metastatic breast cancer are athracycline and taxanes. It is uncertain whether their order of sequence is of importance. There may be differences with regard to rate of response and time to progression (TTP), but this will seldom lead to prolonged total survival.

In Norway, as in many other countries, anthracycline containing regimens have been applied as first line treatment since the eighties, so also today.

Cytostatic treatment is relevant as first-line treatment for metastatic breast cancer when the tumor is estrogen and progesterone receptor negative. If the tumor initially is hormone receptor positive, then cytostatic treatment is appropriate after the endocrine regimens are no longer effective. For HER2 positive tumors, trastuzumab should be administered in combination with cytostatic treatment. It is now more usual that HER2 positive patients are given trastuzumab in combination with a non-anthracycline regimen as first-line treatment. Lapatinib can be used in combination with chemotherapy for patients who have progressed on trastuzumab. 

The treatment of metastatic disease is palliative. However, in many cases, remission can be achieved for several years. Current chemotherapeutic regimens have less side effects  than previous ones.

Brain and bone metastases respond very well to radiation treatment. Bone metastases often also respond well to endocrine treatment.

Indications

Hormone treatment

  • ER and/or PgR positive tumor. When disease development permits to await endocrine response (6-8 weeks) and disease is considered to be endocrine sensitive.

Cytostatic treatment

  • ER and PgR negative tumor
  • Rapid disease development regardless of ER/PgR status
  • ER and/or PgR positive tumor which is not considered to be endocrine sensitive

Bisphosphonates

  • Osteolytic metastases, with or without joint pain (given in addition to cytostatic treatment or hormone treatment)

Goal

  • To control the disease over time
  • Suppress symptoms with as little toxicity as possible
  • Prolong survival if possible

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