Breast cancer: Progress & promise in 2011

The field of breast cancer has been a model for innovation and discovery. The earliest randomized trials were launched in the 1950s to study whether the first generation of chemotherapy could improve curability after surgery. Then the very “out-of-the-box” idea of less radical surgery was tested.

Decades later, the field remains a hotbed of studies to elucidate biomarkers and genetic changes that are the drivers of cancers — and new targets for therapy. Contemporary advances have been made that are producing an immediate impact on the diagnosis and treatment of breast cancer.

In this column, you will learn how less invasive lymph node surgery is proving to be just as effective, with fewer side effects, as more invasive surgery. The latest surprise — that even a positive sentinel node might not necessarily require further node surgery — is still being discussed and interpreted. The “less is better” concept now also involves radiation therapy — even just one day at the time of surgery — may be an option in selected cases.

Improving cosmetic outcomes after breast surgery is the goal of a new fusion discipline called “oncoplastics,” where the skills of breast and plastic surgery combined in one doctor. And nipple-sparing surgery offers women the chance to keep all their skin for reconstruction.’’                 

Breast cancer treatment is moving toward personalized medicine, with gene patterns of breast tumors guiding doctors on the value of chemotherapy, and it appears that fewer patients need to undergo chemotherapy, as science is able to identify those who don’t stand to benefit and will do quite well with hormonal therapy alone.

The most challenging arena in breast cancer is still the management of patients with advanced metastatic breast cancer, where progress has been the slowest. Still, stepwise improvements are being seen in survival with new chemotherapy and biological drugs. In this column, you will learn about the elegant science behind PARP inhibitors and about a drug derived from a marine sponge that has been recently approved by the US FDA.

Read on and find out about the advances that we think are having the biggest impacts on the treatment of breast cancer in 2011.

New drugs, new directions

For women with metastatic breast cancer, some promising treatments include Halaven (eribulin), a newly approved synthetic substance that incapacitates dividing cells, and poly(ADP-ribose) polymerase (PARP) inhibitors, a group of drugs that block repair of single-strand DNA breaks. While these drugs are being tested in a variety of tumor types, in the case of PARP inhibitors, some of the immediate benefit — and buzz — applies to their apparent activity in some women with metastatic, triple-negative breast cancer (TNBC).

Current studies explore how PARP inhibitors work in women with advanced breast cancer who have an underlying BRCA deficiency, says Mark Robson MD, director of clinical genetics at Memorial Sloan-Kettering Cancer Center in New York. PARP inhibitors prevent PARP from initiating the DNA repair process. Unable to repair itself from DNA damage caused by chemotherapy, the cancer cell dies. But normal cells would not be affected since they have normal BRCA function.

For those women with advanced, refractory breast cancer, the other up-and-coming agent that is gaining attention is Halaven. This intravenous drug, derived from the natural marine sponge product halichondrin B, works by crippling microtubules, which is essential to the intracellular scaffolding required for chromosome separation during division.

Some critics are puzzled by the hype but Christopher Twelves, MD, professor at the Leeds Institute of Molecular Medicine in the UK, is enthusiastic about the findings thus far. “Erinbulin (Halaven) is more effective compared to the other ‘real life’ choices for chemotherapy in terms of the likelihood of shrinking the cancer, delaying its progression and also prolonging survival,” he says. Kathy Miller, MD, a breast specialist at the Indiana University School of Medicine, who is cautiously optimistic about PARP inhibitors and other new drugs, sums it all up, as follows: “These drugs are forcing us to think differently of breast cancer — as a group of related but different diseases that happen to occur in the breast.”

According to Miller, distinct breast tumors may need to be treated, diagnosed and even prevented differently. In this context, it’s understandable that some patients, physicians and researchers are encouraged by large studies that demonstrate even small benefits. They believe survival statistics do not tell the whole story. For a small but significant fraction of patients, for example, who may be particularly sensitive to PARP inhibitors, and perhaps to others who respond for other reasons unknown, the difference could be a matter of years.

When less may be best

Many women being treated for breast cancer can safely forego having most of the lymph nodes in their armpit removed, according to new research. This is good news for thousands of women because extensive removal of the lymph nodes (axillary lymph node dissection) can lead to serious complications, such as numbness or chronic arm swelling.

Lymph nodes are small glands that filter lymph — a clear fluid that removes liquids and disease-causing organisms, such as bacteria, from your tissues (see diagram on Page D-1). When breast cancer spreads, the first place affected is usually the lymph nodes located in your armpit. Surgeons once routinely removed these nodes in an effort to halt the spread of breast cancer. Routine removal of the lymph nodes was halted in the late 1990s with the introduction of sentinel lymph node biopsy. This procedure allowed doctors to check just a few lymph nodes for cancer and remove the rest only if those tested were positive.

The new findings, published in the February 9, 2011 issue of the Journal of the American Medical Association, showed that for many women with a positive sentinel biopsy, additional lymph node removal made no difference in survival. It wasn’t the extensive lymph node removal that improved survival, but the follow-up treatment — radiation and chemotherapy or hormone therapy — that mopped up stray cancer cells.

Sentinel lymph node biopsy remains a critical factor in determining whether the breast cancer has spread. The discovery of one or more cancerous lymph nodes generally means that chemotherapy is necessary to eliminate the cancer. “This is an important practice-changing study,” says Mehran Habibi, MD, professor of surgery and oncology at Johns Hopkins Hospital. In fact, the institution has already made changes to its protocol based on the results.

The new findings apply to women with early-stage breast cancer, whose disease has spread to one or two lymph nodes and who are undergoing lumpectomy plus radiation. These women usually receive chemotherapy, hormone therapy or both, in addition to their radiation. The study does not apply to women having a mastectomy, those having a lumpectomy with partial breast irradiation or no radiation, those receiving chemotherapy prior to surgery, or those with three or more cancerous sentinel nodes.

When it comes to extensive lymph node removal, some surgeons may be slow to discontinue a practice that’s been routine throughout their careers. And some women will hesitate to forego the procedure, preferring the idea that they have taken every possible action to eliminate all traces of cancer.

But “less is more” is hardly a new concept in breast cancer treatment. Just as lumpectomy plus radiation has allowed thousands of women to keep their breasts, this study will allow thousands more to keep their lymph nodes.

Breast reconstruction surgery

In one recent study by the American Society of Plastic Surgeons (ASPS), it was found that nearly 70 percent of women who are eligible for breast reconstruction are not informed of the reconstructive options available to them. The ASPS emphasizes that it is a key conversation that should take place at the time of diagnosis.

Rache Simmons, MD, of the Weill Cornell’s Breast Center in New York, says consideration should be given to optimize the cosmetic result with a skin-sparing mastectomy and immediate breast reconstruction. Dr. Simmons has pioneered skin-sparing mastectomy techniques that include the option of reattaching the nipple and areola if an examination indicates there are no cancer cells present. “The option of saving the nipple and areola of the breast allows a dramatically improved cosmetic result with reconstruction,” she explains. Today, in the emerging field of oncoplastic surgery, breast surgeons are undergoing additional training in plastic surgery techniques that allow them — as a single surgeon — to preserve or restore a breast while they perform cancer surgery. This is particularly helpful when the size or location of a tumor requires an oncologic resection that is cosmetically challenging and the patient wants surgery on the other breast for symmetry. As Simmons explained, “While curing a woman’s breast cancer is the most important goal, how the patient looks after surgical treatment has a significant impact on her ability to resume normal life.”

Indeed, the speed of research and changes in breast cancer practice is picking up. This will continue to deliver hope to all those with the most common cancer in women — one that is becoming more curable and treatable every year.