March 26 is a significant day for various reasons, but why depends on who you are. In 1958, the United States Army launched the Explorer 3 artificial satellite.
Sixty years later on that day, Carolyn Graham was diagnosed with breast cancer.
“My worst fears were confirmed,” says Graham, a teacher at Notre Dame High School in Lawrenceville, New Jersey. “I had breast cancer. The following days were a whirlwind of emotions; mainly, I wondered how I was going to tell my kids, my family, my friends and students.”
Graham, who resides in Langhorne, Pennsylvania, was diagnosed with stage 2 invasive ductal carcinoma in the left breast , with evidence of disease in at least three or more lymph nodes.
“I had found a lump in my left breast — two weeks after my annual checkup — and it was painful,” she says. “I went to the doctor and was reassured that it was probably nothing given my age, 38 at the time, and that the lump was causing pain. I went through a series of tests — diagnostic mammogram and ultrasound, biopsies.”
After meeting with a team of doctors, it was decided that based on her diagnosis she would begin with neoadjuvant chemotherapy, which is chemo before surgery. She was placed on a “common cocktail” consisting of the cancer-fighting drugs adriamycin, cytoxan and taxol,” or ACT.
Graham started treatment in April 2018 and finished that August. In October of that year she underwent a bilateral mastectomy with lymph node removal in the left side; then, in November, began 28 doses of proton radiation treatment at ProCure Proton Therapy Center that ended in January 2019. The treatments were pretty standard for women diagnosed with her type of breast cancer.
Upon meeting with the radiation oncologists, her doctor highly recommended proton radiation therapy.
“I had heard of it, but I was not aware of the differences between standard photon radiation and proton radiation,” Graham says. “Because of my age and the risk of photon radiation potentially damaging my heart and lungs, I ultimately decided to go with proton radiation.”
History in the making
According to the American Cancer Society, nearly one in three people will have cancer during their lifetime. But the odds of being cured are greater than ever. Cancer treatment has come a long way over the years, and modern medicine is improving, extending and saving lives.
In the early half of the 20th century, cancer “was generally a death sentence,” says Dr. Nancy P. Mendenhall, associate chair of the radiation oncology department at the University of Florida Health Proton Therapy Institute.
“However, through technology development and clinical trials, significant progress began in the mid-part of the last century,” she says. “The first Cobalt machine was created in 1951. The first evidence of cure of Hodgkin’s lymphoma with radiation therapy was reported about the same time. Three-dimensional imaging was not available until the 1980s and ’90s, so physicians had to make educated guesses as to the extent of cancer, which affected the success rates of both surgery and radiation therapy.”
In the 1980s, more sophisticated radiation equipment provided radiation beams that were better able to reach deep-seated tumors, Mendenhall says, and in the 1990s, with the development of 3-D imaging-based treatment planning and delivery systems, radiation dose distributions could be generated and delivered that conformed more precisely to the cancer target, leading to decreased toxicity and improved disease control.
The 19th century saw the birth of scientific oncology with use of the modern microscope in studying diseased tissues, according to the ACS. In the 21st century, the growth in knowledge of cancer biology has led to remarkable progress in cancer prevention, early detection and treatment. Cancer research is advancing on many fronts, according to the ACS, including more targeted therapies, immunotherapy, gene mutations and cancer genetics, nanotechnology and robotic surgery.
There have been tremendous advances in cancer detection, treatment and prevention over the past few decades that have led to reduced toxicity risks, increased survival and better quality of life in survivors of certain types of cancer, Mendenhall says.
“In cancer detection, these include mammography and magnetic imaging in breast cancer, Pap smear in cervix cancer, and PSA screening in prostate cancer, all of which have been associated with early detection and decreased cancer mortality rates,” she says. “In addition, radiation equipment evolved from delivering only low-energy photons to higher energy photons according to sophisticated computerized treatment planning systems that could more favorably distribute the radiation dose in targets and normal tissues, to the development of proton therapy which actually reduces, rather than simply redistributes radiation dose to normal tissues.”
Dr. Lee Greenberger, chief scientific officer at the Leukemia & Lymphoma Society headquartered in Rye Brook, New York, says we’ve reached “an incredibly exciting and unbelievably productive time” in cancer research since 2000.
“In the past two years alone there have been an unprecedented more than 40 new FDA-approved therapies for blood cancer with many of therapies approved for the first time,” he says.
Greenberger adds that immunotherapy, a cancer treatment that helps the immune system fight cancer, now plays a key role in treatment.
“Two of these therapies, the so-called chimeric antigen receptor T cells, or CAR-T, therapies were approved for certain leukemias and lymphomas in 2017, and history was made when the FDA approved [them]. … Now, researchers are exploring CAR-T cell applications for other cancers, such as lung, breast, colon and prostate,” he says.
Chemotherapy at the forefront
Doctors are also starting to see treatment strategies shift toward a “less is more” approach, according to Greenberger.
“For patients, this means moving away from the physical and financial impacts tied to extensive chemotherapy treatments and toward more targeted therapies, which are increasingly able to pinpoint the root cause of disease and help patients avoid treatments with major side effects. This is the heart of precision medicine,” he says. “We can find these mutations across more than 200 genes in one assay, so the technology has allowed us to rapidly find the target and deploy the new therapy. Chemotherapy-free regimens are also on the rise, with more patients able to take a pill at home rather than go into a hospital or clinic.”
Surgical techniques have become more precise and less disfiguring and invasive, says Amit Kumar, president and CEO at Anixa Biosciences, a biotechnology company headquartered in San Jose, California.
“We have also become better able to deliver radiation, but it is still a blunt tool,” says Kumar, who’s also on the board of directors of the American Cancer Society. “Chemo has also become better with better and more selective agents and more targeted therapies based on a mutational analysis of the cancer.”
In addition, with radiation therapy there has been a dramatic technology evolution leading to improved radiation dose distributions in the patient — e.g., more radiation to the cancer and less to the adjacent organs, she explains.
“To date, most radiation is delivered with machines that deliver radiation beams of photons (X-rays) from an external source aimed at the cancer within the patient,” Kumar says. “With the development of proton-based radiation therapy, it was possible, for the first time, to actually place most of the radiation dose inside the cancer target, rather than outside.”
Chemotherapy has powerful and undesirable side effects, because while it kills fast-growing cancer cells it also destroys or slows the growth of healthy cells that grow and divide quickly. The cells most affected commonly include those that line your mouth and intestines, and make hair grow. The side effects, most commonly fatigue, often get better or go away after chemotherapy is completed.
Breast cancer survivor Graham’s chemo side effects were “pretty standard,” she says. “I was really lethargic for a few days after treatment. It felt like I just ran a marathon while hungover. It would last a few days, then I would bounce back.
Graham had an allergic reaction to taxol and started to go into anaphylactic shock, so had to be treated with the drug abraxane.
"Essentially, the chemo was the same... The side effects were more physical — extreme bone and joint pain that would last for a few days, then dissipate, she says.”
Regarding radiation, Mendenhall says the decrease in acute and late radiation side effects with the development of better technology has been dramatic. One example is in prostate cancer, she says.
“Historically, radiation doses to the prostate for men with prostate cancer were limited by several gastrointestinal and urinary tract toxicity; cure rates were low with radiation and salvage surgery was difficult due to the damage in adjacent bowel and bladder,” she says.
With the development of better linear accelerators, 3-D computerized treatment planning, delivery of intensity modulated radiation dose distributions, and now proton therapy, much higher and effective radiation doses can be delivered safely and salvage surgery, while needed less, is possible, Mendenhall explains. Because of the decrease in radiation damage to normal adjacent tissues, the intensity of radiation delivery has increased and treatment regimens are actually shorter, therefore much less expensive and inconvenient.
Similar developments have occurred with breast and lung cancer, Mendenhall says.
“Proton therapy in particular has enabled the delivery of effective radiation doses to certain cancers with less acute toxicity — e.g., head and neck cancer patients who are much less likely to have weight loss, need hospitalization, or placement of feeding tubes with proton therapy compared to conventional IMRT radiation therapy. Other examples are esophageal and pancreatic cancer.”
Patients treated with proton therapy have less of a risk of radiation exposure to the heart, lungs and healthy breast tissue because protons deposit their energy directly into the tumor and not the tissue behind it. Less radiation to these areas may lower the risk of developing heart disease, lung disease and secondary tumors decades after radiation treatment.
In addition to chemotherapy damaging healthy cells, another major drawback of modern cancer therapy is expense. Whether it be a new chemotherapy agent, a monoclonal antibody or sophisticated radiation therapy, the cost of initial treatment is typically increased.
The importance of screenings
As mentioned earlier, mammograms and magnetic imaging, Pap smears and PSA screenings are all recommended methods of early cancer detection.
The ACS recommends colon cancer and prostate cancer testing for men by age 45 and lung cancer testing by age 55; for women and cervical cancer, starting at age 21 and through age 29, all women should have a Pap test done every three years. At age 30, women at average risk should get a Pap test and HPV test every five years, or they can continue to get only a Pap test every three years. Women ages 40 to 44 should have the choice to start annual breast cancer screening with mammograms if they wish to do so. Starting at age 45, women should get mammograms every year.
Dr. Timothy Byun, medical oncologist at St. Joseph Hospital’s Center for Cancer Prevention and Treatment in Orange, California, is among the numerous medical advocates of screenings for early detection and cancer prevention.
“Many cancer outcomes have improved over the decades of effort to fight cancer,” Byun says. “For example, Hodgkin’s lymphoma, testicular cancer, many pediatric cancers have high rates of cure. Cancer death rate has steadily decreased over time in this country. According to American Cancer Society (Cancer Statistics 2019), the death rate for lung cancer dropped by 48% from 1990 to 2016 among men ... and by 23% from 2002 to 2016 among women. The death rate for female breast cancer dropped by 40% from 1989 to 2016, driven by screening mammogram, improvement in surgery, radiation, and systemic therapy. For prostate cancer, mortality dropped 51% from 1993 to 2016. Colorectal cancer mortality dropped by 53% from 1970 to 2016.”
As for Graham, she says she’s been in remission since her surgery on Oct. 3, 2018.
“I have been declared ‘no evidence of disease,’” she says, however, admits she’s “still trying to figure out what her ‘new normal’ is.
“I have learned that certain things are worth worrying about, and others are not. ... I have also tried to maintain a positive attitude throughout the entire journey. Sure, I have had my down days, but in the end, I have tried to turn this horrible event into something that I can use to pay it forward. Ultimately, I have been able to show others that one can go through hell and survive.”