Medical Advances and Treatment Decisions: A 20-Year Retrospective

Insight Articles
October 18, 2013
By: 
"Mary Alice Hartsock"

Published in the Fall 2011 issue of LBBC's National Newsletter, Insight

When LBBC was founded 20 years ago in response to a woman's need for breast cancer-related information, connection and support after treatment ends, treatment choices were more limited than today. Researchers were just beginning to understand that a one-size-fits-all approach could not effectively treat all breast cancers, and women struggled to incorporate individual options and preferences into decision making.

Today, research developments allow you to consider your lifestyle and career goals as you select treatments and strategies to manage side effects. “The advancements in our understanding of the biology of breast cancer have changed the face of treatment decision making,” says Larry Norton, MD, deputy physicianinfo-icon-in-chief for breast cancer programs at Memorial Sloan-Kettering Cancer Center in New York City. “These discoveries are helping us to understand what treatments could benefit each individual patient.”

Biology and Decision Making

In the past two decades, researchers have learned that cancers have unique geneticinfo-icon profiles that predict how they will grow and what treatments will work best. Previously, mastectomyinfo-icon and chemotherapyinfo-icon were almost always standard treatment.

“When I was diagnosed in 1985, I had very little information on the cancer’s characteristics,” says Claire Parker, 62, of Denver. She needed more surgeryinfo-icon after an excisional biopsyinfo-icon did not remove the entire tumorinfo-icon, but she didn’t want a mastectomy, then the standard of careinfo-icon. After her insurance rejected a recommendation for a lumpectomyinfo-icon from a prominent doctor, Claire could not find a surgeoninfo-icon within her policy willing to perform it.

“The majority of our knowledge 20 years ago was based on what we could see under the microscope—tumor size, gradeinfo-icon and number of involved lymphinfo-icon nodes,” Dr. Norton says.

Today, medical tests performed on the breast tissueinfo-icon and lymph nodes provide information on the behavior of proteins that control our bodies’ cells. If specific proteins are present, absent or malfunctioning,doctors can predict how a cancer will react to certain medicines and tailor your treatment accordingly.

Hormones

Your healthcare team may help you select treatments that target the misbehaving or absent genes in breast cancer cells to slow them down or stop their activity. Unlike chemotherapies, these treatments target cancer cells while avoiding healthy cells. 

The first target identified for breast cancer treatment, the estrogen receptorinfo-icon, led to new treatments for hormoneinfo-icon-sensitive breast cancers. Hormone receptors are proteins that receive messages from hormones in the bloodstream and tell cancer cells to grow.

Hormonal therapies stop or slow estrogen receptor-positiveinfo-icon breast cancer growth by blocking estrogeninfo-icon’s effects or reducing the body’s estrogen levels. In 1977 the U.S.Food and Drug Administrationinfo-icon approved tamoxifeninfo-icon, the first hormonal therapyinfo-icon, to treat ERinfo-icon+ metastaticinfo-icon disease. About 20 years ago, the FDAinfo-icon approved tamoxifen to help prevent recurrenceinfo-icon in early-stageinfo-icon breast cancers. In 1998, it was approved to reduce risk in healthy women.

Ruth Pogarsky, 72, of Lakewood, NJ, was diagnosed with breast cancer in 1984 and 1994. At her first diagnosisinfo-icon, she had surgery to remove a stage I cancer confined to her breast, but she didn’t know her hormone receptorinfo-icon status. After a second lumpectomy in 1994, her doctor learned she had ER+info-iconbreast cancer and prescribed tamoxifen. 

Beginning with hormone-sensitive cancers, “the 1990s saw the dawn of the understanding that a tumor’s biochemical characteristics were more important than its anatomic characteristics,” Dr. Norton says.

In 1995 the FDA approved the first aromatase inhibitorinfo-icon, anastrozoleinfo-icon (Arimidex), for postmenopausalinfo-icon women with ER+ metastatic breast cancer whose disease progressed after tamoxifen. Over the next ten years,additional AIs were approved as long-term treatment for postmenopausal women with early-stage disease and first-line treatment for metastatic breast cancer. Recent studies suggest switching from tamoxifen to an AI after several years may lower recurrence risk in postmenopausal women. Tamoxifen and AIs have also begun to be used for early management of hormone receptor-positive metastatic disease.

“Women with hormone-sensitive metastatic breast cancer didn’t have many treatment options 20 years ago,” says Lillie D. Shockney, RN, BS, MAS, university distinguished serviceassociate professor of breast cancer at John Hopkins University School of Medicineinfo-icon. “Hormone therapyinfo-icon may allow these women to live a longer, healthier life.”

When Helpline volunteer Nancy Clark, of Hendersonville, NC, was diagnosed with ER+ metastatic breast cancer at age 49, the cancer remained stable with tamoxifen and leuprolide (Lupron), a medicine that suppresses the ovaries’ ability to produce estrogen.

Five months later, Nancy decided to switch to anastrozole,an aromatase inhibitor.  She wasn’t satisfied with the cancer being stable, and she had read that anastrozole might offer more benefits. Seven years later, tests continue to show no evidence of cancer.

HER2 and Other Targets

The development of medicines in 1998 that target the HER2 (human epidermal growth factor receptorinfo-icon-2) proteininfo-icon, which in about a quarter of breast cancers is involved in the signals that tell the cancer to divide and grow or not, allows doctors to provide options to many women who do not have hormone-sensitive breast cancers and even some who do, says Dr. Norton.

Medicines that attack HER2 provided choices for Claire when she was diagnosed with HER2 positive breast cancer in 2010.

“Unlike my first diagnosis, I engaged in frank discussion with my treatment team and was given resources for information on targeted treatments and chemotherapy,” Claire says.

When she learned the HER2 signals in the tumor could cause the cancer to grow and recur, she decided to take trastuzumabinfo-icon (Herceptininfo-icon), a targeted therapyinfo-icon that binds to the HER2 receptor on the cellinfo-icon surface and blocks its function. She also had chemotherapy to enhance the medicine’s effectiveness.

The FDA approved trastuzumab for HER2+ metastatic breast cancer in 1998, and in 2006 it was approved in combination with chemotherapy for early-stage, HER2-positive disease. 

Because targeted therapies attack specific pathways and features of cancer cells, they may not cause many of the most feared side effects of chemotherapy, such as nauseainfo-icon, vomiting and hair loss. If you’re taking one, your doctor will need to monitor you for possible heart damage.

Targeted therapies that cross the blood-brain barrierinfo-icon have lengthened life for women with metastatic breast cancer, explains Ms. Shockney. Lapatinibinfo-icon (Tykerbinfo-icon), which blocks the effect of HER2 and a related protein,HER1, by interfering with a pathway inside the cell, is taken as a pill and has limited heart effects. FDA approved lapatinib in 2007, and it is available in combination with the chemotherapy pill capecitabineinfo-icon (Xelodainfo-icon) for metastatic breast cancers that stop responding to trastuzumab.

“Targeted therapies offer a refreshing improvement in seeing how cancer can be treated and managed,” Ms. Shockney says. With additional research, “we will continue to see more medicines created.”

Triple-Negative Breast Cancerinfo-icon

Although doctors did not use the term “triple-negative breast cancer” for hormone receptor-, HER2 negative disease 20 years ago,research revealing the many different types of breast cancer has led to identification of this subtype.

Chemotherapy often provides successful treatment, but researchers hope to find features common among these cancers that will lead to better treatments with fewer side effects. 

Many believe triple-negative cancers are related to proteins and enzymes that cause breast cancer growth. Some triple-negative breast cancers contain Vascular Endothelial Growth Factor Receptor 2, a protein that inhibits angiogenesisinfo-icon, a process by which tumors create new blood vessels to get oxygen and nutrients they need to grow. A protein called Epidermal Growth Factor Receptor (EGFR), which causes tumors to grow when they produce too much of it, also may fuel these cancers. Researchers are studying an enzyme called polyadenosine-disphosphate-ribosepolymerase (PARPinfo-icon), which fixes DNA breaks common in triple-negative breast cancers. Clinicalinfo-icon trials of medicines that block or target these proteins and enzymes are ongoing.

Predictive Testing

Doctors are also working to reduce risk of overtreatment,says Ms. Shockney. Genomic assays, tests that examine whether groups of genes in cancer cells are present, absent or too active, can help determine if hormone-positive cancers need chemotherapy. These assays predict how likely the cancer is to respond to chemotherapy treatment as well as the likelihood of the cancer coming back in the future.

At the 2005 San Antonio Breast Cancer Symposium researchers reported that a genomic assayinfo-icon called OncotypeDX successfully predicted the need for chemotherapy in ER+ disease based on a Recurrence Risk score. Oncotype DX uses a tumor tissue sample to examine activity patterns in 21 genes and predict the likelihood of recurrence within ten years.

In 2007 the FDA cleared another test, MammaPrint, to assess recurrence risk in early-stage, lymph nodeinfo-icon-negative breast cancer. This test,performed on a tumor tissue sample during surgery, looks at the activity of 70 genes to predict whether cancer could recur within five and ten years.

Eileen Frazzetta, of New York City, had a bilateralinfo-icon mastectomy after her diagnosis with early-stage, ER+ breast cancer in 2009 at age 51. Because of the tumor’s size and stage, her oncologistinfo-icon recommended chemotherapy.

The fifth of five sisters to be diagnosed, Eileen was extremely concerned about having problems with thinking and memory because of chemotherapy. “I am a professional person, and I was worried about prolonging the process of getting back to work,” she says.

She suggested OncotypeDX to her doctor, which she “had read about online, and we talked about the benefits and open issues,” Eileen says.

Eileen’s results were not definitive, but they did not suggest a strong need for chemotherapy. She decided to pursue hormonal therapy. She feels confident she made an informed decision based on her test results and goals.

Managing Side Effects

Researchers are developing new ways to reduce chemotherapy side effects and improve everyday life, Ms. Shockney says.

When Etsuko Kagawa,49, of San Francisco, entered a clinical trialinfo-icon for triple-negative breast cancer that included chemotherapy, she took the medicines aprepitantinfo-icon (Emend) and ondansetroninfo-icon (Zofraninfo-icon) to prevent nausea and vomiting.

“I didn’t feel sick at all, and I could continue eating and working,” Etsuko says. “Though I was weak from treatment, support from olleagues was an invisible drug.”

Antiemetics “enable you to work, get a paycheck and keep your health insurance, which will reduce anxietyinfo-icon,” says Ms. Shockney. “Chemotherapy is getting added into your schedule, whereas 20 years ago it took over your life.”

Medicines that build up white blood cellinfo-icon count, like pegfilgrastim (Neulasta), have helped women avoid fever and hospitalization, Ms. Shockney says.

More research needs to be done, she says, to prevent neuropathies (nerveinfo-icon damage), heart problems, issues with thinking and memory and complications from surgery and radiationinfo-icon. Researchers also must find ways to reduce menopauseinfo-icon-like side effects during long-term treatment.

Looking Forward

These advances have provided many new options, but decision making is more complex because all choices have strengths and weaknesses, says Ms. Shockney. Seek information and ask questions until you find a plan that fits your goals and lifestyle.

If you’re a long-term survivor, you might wonder what these changes mean for you.

Ruth, a Helpline volunteer, has stayed up to date on the “dazzling array of choices” available to newly diagnosed women.

“Every day in the newspaper, there’s something new. I’m always wondering, ‘Did I miss out? Did I do the right thing?’ It can be mind boggling to know all of this!” She is diligent with follow-up testing and asks her medical team how new developments could impact her care.

As researchers learn more about the many types of breast cancer and methods to incorporate individual options and preferences into treatment decision making, medical breakthroughs will continue to expand treatment options. This will impact decision making for all women with breast cancer. If you want to help, consider joining a clinical trial. Visit lbbc.org for more information.

More Medical Advances: 1991-2011

1994: Armando E. Giuliano, MD, FACS, reports that sentinellymph node biopsyinfo-icon (SLNB) may be viable alternative to axillary lymph nodedissection (ALND).

2001: Journal of theNational Cancer Institute states bilateral prophylactic mastectomyinfo-icon decreasesrisk of breast cancer by 90 percent in women with BRCA1info-icon or BRCA2info-icon genemutations.

2002: Two studies in the New England Journal of Medicine show lumpectomy plus radiation is as effective as mastectomy against tumors less than four centimeters across.

FDA approves MammoSiteinfo-icon system, a type of accelerated partial breast irradiationinfo-icon that delivers radiation from inside the breast, to treat early-stage breast cancerinfo-icon.

2006: Journal of the National Cancer Instituteinfo-icon reports women who have SLNB have greater arm function and quality of lifeinfo-icon compared to those who have ALND. Doctors recommended SLNB in early-stage breast cancers with clinically negative nodes.

2009: The European School of Oncologyinfo-icon’s Metastatic Breast Cancer Task Force releases new international guidelines, stating that sequential single-agent chemotherapy and combination chemotherapyinfo-icon have similar survival outcomes.

2010: TARGIT study results indicate that radiation given ina single doseinfo-icon directly to the cancer site during lumpectomy is as effective and safe as standard radiation in women over age 45 with early-stage breast cancer.

Canadian study published in New England Journal of Medicine demonstrates that lower-dose radiation given over a shorter time period has similar 10-year recurrence rates as standard radiation therapyinfo-icon.

Study presented at American Society of Clinical Oncology (ASCO) annual meeting suggests that biopsying metastatic disease sites to identify receptor status may change treatment recommendations.

2011: Z0011 trial finds no significant differences in survival or recurrence risk among women with cancer cells in the sentinel node who underwent SLND rather than ALND and who had lumpectomy, systemic therapyinfo-icon and radiation.

Analysis suggests that with more use of internal radiation or high dose rate brachytherapyinfo-icon (putting a radioactiveinfo-icon implantinfo-icon directly inside the body), patterns of radiation treatment use for women age 70 and over with stage I breast cancerinfo-icon are changing, and more women with ER+ breast cancer are forgoing radiation treatment.

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