Breast cancer treatment mainstays of radiation, surgery and chemo evolve.

Less is more.

In many ways, that describes the evolving philosophy of treating breast cancer, a disease that has affected the lives of3 million US women.

Increasingly, cancer specialists say, their aim is to treat the cancer successfully while minimizing or avoiding unnecessary surgery, radiation or potentially toxic drugs that can have lifelong effects.

“We've come a very long way in the last 25 years from very aggressive treatment to where we are today,” says Shilpa Padia, MD, co-medical director of Breast Cancer Services for Mount Carmel Health System. “Our goals in treatment are for women to continue to be who they are and not just a breast cancer patient.”

Padia and other local cancer specialists say advances in treatment have kept pace with the substantial increases in breast cancer research funding over the last few decades. “So much changes just in one year,” Padia says. “People are clearly thinking outside the box.”

Of all cancers, breast cancer receives the lion's share of funding.

According to Susan G. Komen, the federal government now devotes more than $850 million each year to breast cancer research, treatment and prevention—compared to $30 million in 1982. That's in addition to funding from other sources. Komen estimates it alone has invested more than $2.5 billion.

William Farrar, MD, interim physician-in-chief at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, says funding has led to quantum changes in the way specialists approach breast cancer.

In the last 30 years, Farrar says, “We have made tremendous advances in surgery, in chemotherapy and in radiation. Those are the direct result of clinical research.”

The mainstays of breast cancer treatment—surgery, chemotherapy and radiation—still are the key players; however, their roles are changing and, in some cases, no longer required.

No Two Alike

Breast cancer specialists are learning that the disease often is quite different from woman to woman. Expanding knowledge of cell growth, the biologic characteristics of tumors and genetic factors that control cancer can lead to far more tailored treatment.

“They're exciting advancements,” says Natalie Jones, MD, a surgical oncologist with OhioHealth. “We no longer have to lump all women together. It is becoming more personalized medicine.”

Jeanna Knoble, MD, also co-medical director at Mount Carmel, says, “There is a growing realization that breast cancer is such a heterogeneous disease. It can be confusing for women if a friend or neighbor received one treatment and they are getting a different protocol, but each woman's cancer is so unique.”

Here's a look at what has been trending in the multi-faceted campaign to treat a disease that can be equally complex:

Surgery

Not that long ago, a breast cancer diagnosis meant radical mastectomy: complete removal of the breast, chest muscle, sections of the chest wall and all lymph nodes. The surgery was disfiguring, painful and left both physical and emotional scars.

The advent of lumpectomies (removing just the tumor) followed by radiation was a major step forward and yielded equivalent survival rates. The next frontier involved sparing lymph nodes when possible, thereby mitigating serious side effects such as lymphedema, a collection of fluid leading to swelling in the arms and legs.

It's now possible to perform sentinel biopsies using radioactive dye to show which lymph nodes are most likely to contain cancer cells. Only those lymph nodes that take up the dye are removed for further testing at the time of surgery, and that has spared about 60 percent of patients from having all nodes removed, Farrar says.

Even more exciting is the notion of avoiding surgery altogether. In research being conducted across the country, investigators are studying women who have a complete response to chemotherapy when it is used as a first-line treatment.

“We've gone from women having radical mastectomies to the possibility of no surgery,” Farrar says. “That's a huge change.”

Chemotherapy

Like surgery, advances in drug treatment of cancer mean that medical therapy no longer has to be as debilitating as the disease itself.

Generally, breast cancers fall into three categories, and where they fall often determines a course of treatment:

• Hormone receptor-positive cancers are affected by the hormones estrogen or progesterone. These can be treated using hormone-blocking therapy such as tamoxifen, which can spare women from toxic, traditional chemotherapy drugs. Agents called aromatase inhibitors lower estrogen levels by stopping an enzyme from converting hormones to estrogen.

• Another cancer subtype, known as HER2-positive, indicates a higher-than-normal level of a protein that promotes cancer cell growth. It now is treated with the biologic agent Herceptin and other medications.

• Triple-negative cancers are not affected by estrogen, progesterone or the HER2 protein. While they do respond to therapy, they also are more aggressive and likely to recur.

Aggressive cancers now also can be treated with neoadjutant therapy, where chemotherapy is administered first. Used most often in triple-negative cancers, the goal is to reduce tumor size so that surgery is less complicated.

A newer, valuable piece of information guiding treatment is found in oncotype scoring, which examines tumor DNA to classify the cancer as having a low, high or intermediate risk of recurring.

“With the advent of oncotype and other testing, we can identify patients who clearly need chemo. … We've gone from almost everyone getting it to only those who need it,” OSU's Farrar says.

Cancer treatment choices can be complicated, according to Padia. “Women are happy to have information. When women can see those numbers, it helps them make a decision.”

Radiation

As with surgery and chemotherapy, radiation to kill cancer cells can cause collateral damage and also can be associated with increased cancer risk. With that in mind, specialists focus on mitigating the amount of radiation a woman is exposed to during treatment. Sometimes they try to avoid it altogether.

At the James, women who meet eligibility criteria—about 60 percent of patients—can have prone radiation, in which the patient lies on her stomach, rather than on her back, as is the traditional approach. The breast falls away from the chest wall, and radiation is delivered from underneath. That reduces radiation exposure to the lungs, chest and heart wall, Farrar notes. Because it is more complicated to perform, only larger centers might have the technology and trained personnel to deliver it, he adds.

Accelerated partial breast irradiation is a localized form of radiation treatment (brachytherapy) that involves the insertion of a radioactive “seed” to kill breast cancer cells that might remain after lumpectomy surgery.

APBI is delivered via catheter twice a day over a period of five to seven days, compared to external beam radiation, which usually involves daily treatments five days a week for four to six weeks.

The radiation dose is concentrated on the tissue surrounding the lumpectomy cavity, sparing normal tissue and organs from unnecessary radiation.

A newer approach, currently used at Mount Carmel, involves a one-dose application of Intraoperative Radiation Therapy. The single dose is delivered over a period of about 20 minutes at the time of surgery. Qualified candidates generally are women between the ages of 65 and 70 with hormone-positive, stage 1 cancers, Padia says. In addition to reducing the amount of radiation exposure, IORT also can help with compliance, particularly among women who have to drive long distances to receive therapy.

Looking Forward

Experts agree that the future of breast cancer treatment will involve zeroing in on the exact nature of a woman's cancer, gauging how well it will respond to specific treatments and determining how likely it is to recur.

Toward that end, Farrar says, work continues on the identification of specific cancer subtypes. For example, a certain portion of women with triple-negative cancers experience recurrences in two to three years, “and (the cancer) comes back in a terrible way, with metastases everywhere. We want to be able to pinpoint which ones are going to be really aggressive so we can better tailor therapy.”

Clinicians also place high priority on identifying additional biologic agents that specifically disrupt the tumor's makeup rather than kill cells indiscriminately.

Recent research has focused on immunotherapy, which uses the body's natural defense system to combat cancer. One area in particular involves tumor-infiltrating lymphocytes, white blood cells that migrate to tumors.

Studies have suggested that patients with robust levels of these lymphocytes might respond better to treatment. The goal is to manipulate them in order to achieve better outcomes, Farrar says.

Laurie Loscocco is a freelance writer.