Coffee with Komen – Metastatic Breast Cancer

by Kathy Miller, MD

In the fight against breast cancer, metastatic disease is an important topic to understand. So, what exactly is it?

Metastatic breast cancer (also called stage IV or advanced breast cancer) is breast cancer that has spread beyond the breast to other organs in the body (most often the bones, lungs, liver or brain).

In the U.S., it is not common to have metastatic breast cancer when you are first diagnosed. It usually develops when the cancer returns at some point after the initial diagnosis and treatment.

Metastatic breast cancer is generally incurable with an average survival of 18-30 months. While the average is accurate, there is a very large range and most patients aren’t average. Some long-term survivors (albeit with disease) can be expected even in the absence of effective treatment.

What do we mean by “generally incurable?”  Is long-term disease-free survival ever an attainable goal for patients with metastatic breast cancer?  Investigators at M.D. Anderson reviewed the long-term follow-up of 1,581 patients receiving initial chemotherapy between 1973 and 1982. Two hundred sixty-three (16.6%) patients achieved a complete response (CR); 49 (3.1%) patients remained in CR for 5 years or more.

Treating metastatic breast cancer

Can we predict which patients are likely to be long-term survivors who therefore might benefit from aggressive initial therapy? Yes, but to a limited degree. The long-term CR group had more premenopausal patients, a younger median age, fewer sites of disease and fewer symptoms of disease.

Should all patients be treated aggressively, with the hope of curing them, in the knowledge that only a few will be saved? Should treatment focus on minimizing symptoms at the potential expense of the few who may see long-term benefits from aggressive therapy? Although these goals are not mutually exclusive, there are no simple answers. Nor can (or should) the physicians make this decision independent of the patient. A patient’s desire to attend a child’s wedding on a given day is quite real and important and should be respected – regardless of the adjustments to the chemotherapy schedule that may be required. 

An often overlooked, but crucial, component of the treatment of metastatic breast cancer is the role of supportive services. Social workers may arrange home care, disability payments, and compassionate use drug discounts. Clinical psychologists may bolster coping skills to decrease the effect of depression and anxiety. Legal assistance may be required to provide for minor children. Spiritual counselors may provide hope when drugs fail.  Only in an open, multidisciplinary environment and with frank discussion of the nature of the disease and goals of therapy can optimal treatment be delivered.

Breast cancer has a more varied course than most other common cancers. That’s not surprising when you realize that breast cancer is not one disease. It is a collection of diseases that all occur in the breast. Some are sensitive to hormones, others not. Some have extra amounts of the Her2 growth factor, others not. Some patients develop evidence of metastatic disease shortly after (or at the time of) diagnosis, while others may not experience symptoms of recurrent disease for more than 20 years. Patients are different too. What looks like the same cancer in a different patient may require different treatment. Given all these important differences, we’ll focus on generalities and an approach to treatment rather than specific treatment regimens.

Therapeutic approaches

Generally speaking, two distinct therapeutic options are available for metastatic breast cancer patients:

  • local therapies such as surgery, radiation, hyperthermia or photodynamic therapy
  • systemic therapies such as hormonal manipulations, cytotoxic chemotherapy or specific antibodies targeting HER2.

Local therapies are limited to the specific part of the body treated (i.e.: radiation field, area of tumor resected) and do not affect areas of disease outside the target field.  Considering metastatic breast cancer as a systemic disease may lead us to discount the importance of local therapy – to the detriment of our patients. Prioritizing local and systemic treatment requires an honest assessment of the consequences of uncontrolled local disease and the severity of the disease.

Local therapies can manage symptoms with improvement typically faster than that obtained with even the most effective systemic therapy. For instance, a patient with a solitary painful bone metastasis causing impending fracture and asymptomatic lung nodules might best be treated with surgery and radiation to the bone lesion, followed by systemic therapy. Alternatively, a patient with the same bone lesion and rapidly progressive lung disease causing shortness of breath might be treated with pain medication, limited weight bearing and cytotoxic chemotherapy.

The choice of systemic treatment is based on dual considerations – the probability of response and the toxicity of the therapy. The ‘most aggressive’ therapy is not always the most appropriate or optimal.

We’ve learned a lot about how ER+ disease can become resistant to hormone therapy. That has led to several new therapies that make hormone therapy more effective for a longer time. They do add some side effects and cost, but for most patients the side effects are much less than with chemotherapy.

HER-2 is a growth factor receptor that is overexpressed (or amplified) in approximately 25% of breast cancers and results in a greater risk of recurrence and shortened overall survival – or at least it did before we developed therapies that specifically target the HER2 growth factor. For patients with HER2+ disease, inhibiting HER2 is the most important component of therapy. HER2 treatment can be given at the same time as chemotherapy or hormone therapy, or may be given by itself.

There is no clearly established ‘first’ or ‘second’ chemotherapy regimen. Instead, the choice of chemotherapy must factor the expected toxicity, the patient’s opinion about the severity/importance of those toxicities, interaction with other health problems, and the patient’s prior therapy. For most patients, the increased toxicity and more complicated treatment schedules often associated with combination cytotoxic therapy is difficult to justify.

When deciding how long a metastatic breast cancer patient should be treated with chemotherapy, it’s important to strike a balance between potential benefit and ongoing toxicity. While continuous treatment prolongs the duration of remission, it is not without toxicity and has a minimal effect at best on overall survival. Rather than making definitive recommendations for or against maintenance therapy, the skilled clinician is guided by patient preference and opinion regarding the balance of potential benefit and extended toxicity.

Finally, the option of not continuing systemic therapy should be considered at each point a new treatment is required – whether due to disease progression or unacceptable toxicity with the prior therapy. Rather than a sudden shift in the goals of treatment (from cure to palliation), this recognizes the reality that chemotherapy may no longer accomplish the goal of helping the patient ‘live longer and better.’ Patients, their families and physicians may not reach this conclusion at the same point. Having an open and honest dialogue regarding the patient’s symptoms, hopes and fears can facilitate an optimal treatment plan and an appropriate referral to a hospice or palliative care program.

Clinical trials

There has never been a more exciting time in breast oncology. Years of painstaking basic laboratory investigation have expanded our knowledge of breast cancer biology and allowed the first rationally designed, targeted therapies to enter the clinic. Interference with growth factors offers real promise of more effective, less toxic, individualized treatment. Certainly, other unique, biologically based therapies (anti-angiogenics, vaccines, tyrosine kinase inhibitors, gene therapy) will follow.

Though the excitement and potential are real, progress will be slow as long as only 3-5% of adults with cancer participate in clinical trials. Please ask your oncologist if there is a clinical trial available whenever you need to change treatments. Information about clinical trials for metastatic breast cancer patients can also be found here.

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