Tailored and Targeted
How breast cancer treatment has become more conservative and more effective
By Kasey Fuqua
Treatment for breast cancer has come a long way from mastectomies and broad-spectrum chemotherapy. Thanks to new research and clinical trials, treatment has become more personalized — and conservative — than ever, improving not only survival rates but quality of life throughout survival. For the nearly 235,000 people diagnosed with breast cancer in the United States each year, these advances can’t come soon enough.
“The ability to individualize the treatment plan to each patient and the biology of their tumors has been the biggest advance in breast cancer treatment in the last decade,” says Brian King, MD, breast surgeon at Sentara Surgery Specialists. “Patients are getting smaller operations and less treatment and still have great outcomes.”
Genetic Testing and Identification of Cancers
Like all cancer treatment, breast cancer therapies have become more individualized thanks to the availability and effectiveness of genetic testing. The American Society of Breast Surgeons recommends that every newly diagnosed breast cancer patient should be offered genetic testing, whether or not they are considered high risk for BRCA1 or BRCA2 genes.
“Genetic testing is critical for anybody who presents at a young age or with a strong family history for breast cancer,” says Michael Danso, MD, medical oncologist at Virginia Oncology Associates. “In that population of patients, there’s a significant chance of finding a gene mutation, particularly BRCA1 and BRCA2.”
Breast cancer treatment teams use two different tests to develop a genetic profile of cancer: Oncotype DX, which checks for more than 20 genes, and MammaPrint. Together, these tests help physicians determine who is at most risk for the development of metastatic cancer.
“These tests are being used more and more now to tell us who doesn’t need chemotherapy,” says George Kannarkat, MD, medical oncologist at the Peninsula Cancer Institute. “As scary as cancer is, I think chemotherapy is just as scary to most people. If we can avoid chemotherapy in more women, that would be great.”
Understanding gene mutations in breast cancer patients can shape their entire treatment strategy, Dr. Danso says. It can determine what type of chemotherapy they receive, whether they receive therapy before or after surgery, or even if they receive chemotherapy at all.
“On molecular level, knowing more about the particular disease somebody has allows us to give them the right type of therapy rather than the therapy that is for all patients,” says Dr. Danso. “There are sometimes molecular profiles that suggest a better outcome such that you don’t need to give chemotherapy.”
Having specific gene mutations may also open the door to more treatment options. ADP-ribose polymerase (PARP) inhibitors are approved to treat patients with HER2 negative metastatic breast cancer if they have a BRCA mutation. These treatments prevent DNA repair in cancer genes, leading to cancer cell death. In clinical trials, including those offered at Virginia Oncology Associates, PARP inhibitors extended progression-free survival time by an average of three months.
Women with other gene mutations may also have access to more targeted therapies. For instance, women with PIK3CA mutations and estrogen receptor positive breast cancer benefit from both anti-estrogen therapy and newly approved PIK3CA inhibitors. In trials, these inhibitors extended progression-free survival by nearly six months.
“Our hope is that eventually we can find a targetable mutation in every breast cancer that we can exploit with some drug rather than using chemotherapy,” says Dr. Kannarkat. “We’re getting there slowly, perhaps one gene at a time.”
“Individualized therapy is the future of breast cancer therapy,” says Dr. Danso. “Down the road, molecular profiling may be able to determine whether patients need radiation or even surgery.”
Researchers are also studying the benefits of other testing, such as circulating tumor cell assays. These tests check for tumor cells that are flowing through the blood, providing a less invasive sort of biopsy. They are still being studied and currently not available for routine use.
More Treatment Options for Metastatic Cancer
While targeted and hormonal therapies have been used in breast cancer treatment for several years, breast cancer patients have only recently had access to immunotherapy treatment options.
“It’s hard for a new breast cancer drug to come out and show major improvement on the treatments we already have,” says Dr. Kannarkat. “Thanks to screenings, most of the time we are catching stage 1 or 2 cancers that will be cured 90 percent of the time.”
For patients with more aggressive subtypes of breast cancer or metastatic disease, however, immunotherapy has shown benefits. In patients with HER2 positive cancer, trastuzumab, given with neoadjuvant chemotherapy, increases the chance of a complete pathological response to up to 80 percent. Even after surgery, the use of trastuzumab and chemotherapy is better than chemotherapy alone.
“The most exciting clinical trial we’ve recently been involved in at Virginia Oncology Associates is the use of immunotherapy in triple negative breast cancer,” says Dr. Danso. “The combination of neoadjuvant chemotherapy and immunotherapy showed a significant improvement. The pathologic complete response rate almost doubled in a large randomized trial.”
Triple negative breast cancer is one of the most aggressive forms of breast cancer, with few treatment options until recently. It also affects a greater proportion of patients in Hampton Roads than nationally, “We are participating in multiple clinical trials to better understand and treat this cancer,” says Dr. Danso. “We appear to be making significant strides.”
In addition to immunotherapy, other drug classes are extending survival time for metastatic breast cancer. CDK4/6 inhibitors interrupt cell division and growth in estrogen receptor positive metastatic breast cancers. The oral drugs help patients avoid or delay chemotherapy altogether by stopping cancer progression.
“Patients can sometimes avoid harsher chemotherapy for several years,” says Dr. Kannarkat. “While these drugs have some side effects, they are not nearly as tough as chemotherapy usually is.”
These drugs can also prevent damage to bone marrow cells when patients do receive chemotherapy, allowing oncologists to deliver higher and more effective doses of chemotherapy drugs. Patients who received these drugs with chemotherapy had longer survival times, despite their metastatic or aggressive cancers.
Highly Targeted Radiation Therapy
It’s not just chemotherapy that has become more targeted; radiation therapy has changed dramatically over the past few decades to reduce side effects while boosting effectiveness.
“The difference in the radiation oncology delivery systems of the past and now is the difference between a dial-up phone and the iPhone 10,” says Michele Nedelka, MD, radiation oncologist at Bon Secours Cancer Institute. “Radiation targeting today is far more technologically advanced and precise.”
The precision technology allows radiation oncologists to minimize the dose of radiation delivered to the heart and lungs while maximizing the dose delivered to the breasts. The patient can be tilted or moved millimeter by millimeter to ensure that when they receive treatment, they are perfectly aligned. Respiratory gating also uses special devices to recognize patient breathing and only deliver radiation while the breath is held, which is especially important when treating a left-sided breast cancer because of the proximity to the heart. These tools protect the heart from radiation, reducing a patient’s risk for radiation-related heart damage in the future.
Proton therapy also provides incredibly precise radiation treatment. Unlike external beam radiation, proton therapy does not have “exit doses” that deliver radiation energy along the path to the tumor and beyond. Proton therapy may be particularly beneficial for patients with cancer in their left breast, in order to reduce the risk of damage to the heart and lungs, or for patients with early stage, small breast tumors.
“Proton therapy’s effectiveness in the treatment of breast cancer is rooted in the way the dosage is administered; the beam doesn’t penetrate the chest wall,” explains Allan Thornton, MD, Radiation Oncologist with the Hampton University Proton Therapy Institute. “This significantly decreases and oftentimes eliminates the chance that a patient will suffer from heart disease years after receiving treatment.”
Many patients undergoing proton therapy and even external beam radiation therapy for breast cancer can also receive fewer treatments than ever before. Many patients now undergo four weeks of treatment, instead of six weeks. Certain patients with earlier stage breast cancer may also qualify for brachytherapy, which delivers internal radiation to the biopsy cavity.
“For brachytherapy, you remove the tumor through partial mastectomy and then in the cavity that remains, you place a special catheter,” says Dr. King. “The radiation oncologist can send a radioactive seed down and deliver radiation inside that cavity.”
Brachytherapy patients receive radiation twice a day for just five days and then have the catheter removed. Dr. King says in addition to convenience, brachytherapy can have significant cosmetic benefits in women with darker skin. Brachytherapy removes the risk of hyperpigmentation without changing patient outcomes.
Another type of new brachytherapy offered at Bon Secours, MicroSeed, uses low dose rate radioactive seeds to destroy any remaining cancer cells in the breasts.
“They are small, radioactive pellets like the seeds used in prostate cancer,” says Dr. Nedelka. “We can implant them in one setting in our radiation operating room, and the patient returns home with the implanted permanent seeds.”
While patients must meet stringent criteria for this one-time treatment, it’s just another way targeted care makes treatment more convenient.
More Conservative Surgical Treatment
Thanks to genetic testing, targeted therapies, and advanced radiation therapy, breast surgeons have also been able to change how they deliver treatment. Many patients can now undergo more conservative surgical treatment and experience the same survival and cure rates.
“Over the last decade, there have been more and more studies that show we have been overly aggressive with some of our therapies in how much tissue we removed and how many lymph nodes we removed,” says Dr. King. “What we’ve realized is in select patients, it is a safe option to do less surgery, and those patients do well.”
One of the largest areas of improvement for breast cancer surgery is a reduced need for lymph node dissection. Sentinel lymph node biopsy, which has been performed for many years, has lowered the number of complete dissections by helping surgeons identify which lymph nodes were most likely to be affected by spreading cancer cells. Surgeons now remove just two or three lymph nodes, if any, instead of ten to 12.
“For patients, there is significantly lower risk of lymphedema in the arm or breast, post-operative pain, and injury to any nerve structures that may lead to numbness in the arm or, in rare cases, some weakness,” says Dr. King.
Neoadjuvant chemotherapy has also reduced the need for lymph node dissection for patients with locally advanced cancer or large lesions.
“Historically, surgery was always the first treatment,” says Rachel Burke, MD, FACS, breast surgeon with EVMS Medical Group. “Today, we’re doing a lot more neoadjuvant therapy in triple negative and HER2 positive breast cancers. While there’s no proven survival benefit to doing chemotherapy upfront, it can help people become candidates for breast conserving treatment.”
Biopsy techniques have also rapidly changed from excisional localized biopsies to core needle biopsies to image-guided biopsies with vacuum assistance.
“Instead of repeatedly sticking the needle in, new biopsy machines allow you to take multiple biopsies without withdrawing and reinserting the needle,” says Antonio Ruiz, MD, breast surgeon at Chesapeake Regional Medical Center. “That’s a great improvement in core biopsy techniques for the patient.”
Improved surgical techniques are also allowing women to keep more of their own tissue than ever before, even in the case of mastectomies.
“In years past, we were taking large areas of skin with the breast tissue,” says Dr. Ruiz. “We started doing skin-sparing mastectomies. Now we’ve moved onto nipple-sparing mastectomies, saving essentially the entire breast envelope.”
These nipple- and skin-sparing surgeries provide both a cosmetic and emotional benefit to many women. Surgeons can also boost cosmetic results by carefully placing incisions in the axillary or intramammary creases, called hidden scar surgery, by using tunneling techniques to reach the surgical sites.
“We are trending more towards nipple-sparing surgery almost exclusively,” says Beryl Brown, MD, FACS, breast surgeon and general surgeon with Coastal Surgical Specialists, a Bayview Physicians Group practice. “Not only is it cosmetically superior than building a nipple with 3D tattooing, it is preferable for patients to retain their own nipples. The cosmetic result is excellent, and the oncologic procedure is still superior.”
A great breast surgery begins with careful planning during the biopsy stage thanks to new tools like the SAVI scout electromagnetic reflector. This non-radioactive seed can replace guidewires and radioactive seeds in helping guide the surgeon to the surgical site.
“You can place a reflector in the area of interest, place a hidden scar, which can be in the location of the surgeon’s choosing, and tunnel to the cancer area using lighted retractors,” says Dr. Brown. “This technology enables you to tell how many millimeters you are away from the cancer site so you can get a good margin and decrease the need for a second surgery.”
Even as surgical techniques and technologies improve, the need for breast surgery may be declining.
“The future of surgery in breast cancer is less and less surgery,” says Dr. Ruiz. “With these huge advancements in the medical field, the hope is that need for surgery is going to decrease more and more.”
In Europe, several clinical trials are underway to use more minimally invasive approaches to destroying breast cancer cells. These trials use heat or cryotherapy to destroy tumors without surgical removal. Others are using ultrasound technology to break up cancer cells. Still, most patients in these trials are undergoing surgery after the trial is complete to see how much cancer remains.
“One problem with these techniques is how to prove that you’ve completely destroyed the tumor,” says Dr. Ruiz. “These procedures are primarily being performed through research studies at this time.”
Advances in Reconstructive Breast Surgery
In addition to hidden scar surgeries, advances in plastic surgery techniques have helped patients achieve better cosmetic results after mastectomy or lumpectomy. The early involvement of a plastic surgeon in treatment planning gives patients more cosmetic treatment choices, including skipping reconstructive surgery altogether.
“When we are doing lumpectomy, there are some more basic techniques we can use to improve the cosmetic outcome and wouldn’t necessarily get a plastic surgeon involved,” says Dr. Burke. “We can rearrange breast tissue after lumpectomy to offer breast conservation and give them a good cosmetic result as well.”
For the opposite breast, women may have a small breast reduction or breast lift to maintain symmetry.
In women who receive mastectomies, newer techniques, such as a deep inferior epigastric perforators (DIEP) flap, allow for natural-feeling breasts while preserving muscle tissue in the abdomen and back. These procedures reduce a woman’s future risk for hernias. Women who undergo skin- and nipple-sparing procedures may also benefit from the use of expanders and implants instead of transfer of their own tissue.
From genetic testing to surgical techniques, each aspect of breast cancer treatment has dramatically improved in just a few years. Patients, even those with advanced and aggressive cancers, are seeing extended survival and improved quality of life during survivorship. And thanks to ongoing research, more treatment options are likely only months away.
“We do a great job of curing breast cancer,” says Dr. Nedelka. “My hope, and my strong belief, is that in my lifetime we are going to move metastatic breast cancer from something people die of, to something people die with. I believe that hope is on the horizon.”