THE CANCER ALMANAC

For decades, science has classified cancers by the organ or system in which they begin. That taxonomy is slowly being replaced — but it’s still the indispensable way to understand the odds.

1. Photo

   

   CreditIllustration by Cristiana Couciero

   In the midst of a genetic revolution that promises to scramble everything we know about cancer and how to treat it, our experience of the disease today still begins with a single question: Where did it start?

   That, it turns out, remains a very useful question to ask. The practice of categorizing cancer according to its point of origin within a specific organ or system grew from decades of steady discoveries made by researchers staring at stained slides under a microscope. The shape of cancer cells, they found, would often give clues about a cancer’s behavior. Broken down and sorted by appearance — some cells might be flatter, some are shaped like rings, some look more like oats — cancers were treated differently, and treatment improved. Even as doctors move to the precision of genetic research, the knowledge gained by staring at cells continues to be crucial to treatment.

   Just 10 cancers — in eight organs, the blood and the lymphatic system — will account for more than 70 percent of new cancer cases in the United States this year, according to estimates from the American Cancer Society. The following pages list cancers in order of occurrence — the most frequently occurring first — along with an estimate of the number of deaths that the cancer will cause this year, and its five-year relative survival rate (as compared with people without cancer).

   As we get better at screening for cancers, survival rates improve — the five-year relative survival rate for all cancers diagnosed from 1975 to 1977 was 49 percent in the United States; from 2006 to 2010, it was 68 percent. But numbers don’t tell the whole story. Because doctors are better at finding cancer, treatment improves, but so do incidence rates. And of course, as doctors become better at curing other ills, they allow cancer — the enemy that lurks within the body’s own processes — many more years to strike.

2. Photo

   

   BREAST

   CASES: 249,260 • DEATHS: 40,890 • SURVIVAL: 90%

   Lumps in breasts are common, and caused by a variety of factors, including tumors. Most often, tumors begin in the lobules (the cells that produce milk) and the ducts connecting the lobules to the nipple. The tumors are usually benign, meaning that they will remain in situ (stably surrounded by the tissue in which they were first formed) and cause no harm. Some tumors continue to expand, though, invading neighboring tissue. These are malignant. Breast cells, like all cells, use receptors to convert chemical signals into actions within the cell. These receptors are now seen as defining features of breast cancer, and how they behave is a key factor in determining the most effective treatment.

   ER- or PR-positive: Normal breast cells and some breast-cancer cells contain receptors that attach to the hormones estrogen and progesterone, which can fuel the growth of a tumor. Breast cancers that are ER- (estrogen receptor) or PR- (progesterone receptor) positive will respond to hormone treatment, which can block the estrogen or progesterone receptors. About 74 percent of all breast cancers are ER- and/or PR-positive.

   HER2: Another receptor, for a protein called HER2 (for human epidermal growth factor receptor 2) also spurs cell growth. HER2-positive cancers are more aggressive than HER2-negative ones, but they are also more sensitive to certain drugs that block the HER2 protein. (In cancer, sensitivity is a good thing. The more sensitive the cancer is, the more likely it is to respond to the treatment.)

   Triple negative: Researchers call cancers with none of the above receptors “triple negative.” Such cancers, about 12 percent of all breast cancers in the United States last year, tend to spread quickly and are harder to treat. They are also nearly two times as common in black women as white women, and more common in women with mutations along the BRCA1 tumor-suppressor gene.

3. Photo

   

   LUNG

   CASES: 224,390 • DEATHS: 158,080 • SURVIVAL: 18%

   Lung cancer accounts for one in four United States cancer deaths, in large part because the complex structure of lungs makes tumors both hard to detect and more likely to spread. Only about 16 percent of the tumors are found before metastasis, when their cells have entered the bloodstream or lymphatic system and taken root somewhere else.

   Small-cell: Sometimes called oat-cell, because the cells appear flattened (they contain very little cytoplasm, the liquid inside cells), small-cell lung cancers usually form inside bronchi (the lungs’ branching airways) and are notably aggressive, metastasizing with alarming speed. They appear almost exclusively in the lungs of smokers.

   Non-small-cell: As many as 90 percent of all lung cancers are non-small-cell, and about 40 percent of those are adenocarcinomas, a type of carcinoma (the most common type of cancer) that starts in cells that secrete mucus and other substances (“adeno” is from the Greek for “gland”). About 25 to 30 percent of non-small-cell lung cancers are in the flat cells of the bronchi’s epidermoid lining — squamous-cell carcinomas. Most of the rest are lumped into a category called large-cell carcinomas.

4. Photo

   

   Source: National Cancer Institute CreditIllustration by Cristiana Couciero

5. Photo

   

   PROSTATE

   CASES: 180,890 • DEATHS: 26,120 • SURVIVAL: 99%

   Catching prostate cancer early can save lives, but early detection also presents complicated questions about how to weigh the risk of cancer against the risks posed by treatment. Many prostate cancers grow slowly and might never cause any significant harm; the treatment for prostate cancer, for its part, can cause several undesirable side effects, including incontinence and impotence. There are no clear answers or well-defined lines, so the American Cancer Society recommends that beginning at age 50, men should have a conversation with their doctors about prostate screening, and that those at higher risk — black men or men with a close relative whose cancer was diagnosed before age 65 — should have this discussion beginning at age 45.

   Adenocarcinomas: More than 95 percent of all prostate cancers form in the gland cells of the prostate, but even within this subcategory, the cancer cells can take different forms. Some are described as foamy, others as colloid, still others as signet-ring, because their nuclei are pushed to the periphery in a way that makes them look like the face of a ring. Pathologists use a grading system to determine how well or poorly differentiated the cancer cells look under a microscope (as with many other cancers). Well-differentiated cancer cells get a low grade — they look more like healthy cells. Poorly differentiated cells score higher and tend to spread more aggressively.

   Small-cell carcinoma: An aggressive form of prostate cancer that is difficult to detect because, unlike adenocarcinomas, it does not usually affect the production of a certain protein (called PSA) that shows up in blood samples. It’s made up of small, round cells — hence the name.

   Squamous-cell carcinoma: This type of prostate cancer is nonglandular — it affects the lining of the prostate, and it, too, is hard to detect, because PSA levels typically remain the same. It is very aggressive, with a median survival rate after diagnosis of just 14 months, but also quite rare (less than 1 percent).

   
   

6. Photo

   

   COLORECTUM

   CASES: 134,490 • DEATHS: 49,190 • SURVIVAL: 65%

   Colon cancers nearly always grow slowly, over the course of 15 or 20 years, and usually emerge out of small, already-formed clumps of cells called polyps, found in the mucus-producing gland cells that line the colon. About a third to half of all individuals worldwide have polyps in their colons, but fewer than 10 percent of those polyps will become invasive cancer — adenocarcinomas. Doctors typically determine how advanced the adenocarcinoma is based on differentiation. Differentiation in biology is the process of immature cells maturing, and cancer cells often look like younger versions of healthy cells: The more poorly differentiated the tumor cells are, the more advanced the cancer. Some of the drug therapies used to attack cancer push these younger-looking cells into maturity.

   Vascular invasion: Cancer cells that have moved into the colon’s veins or arteries are a vascular invasion; a lymphatic invasion occurs when the tumor has entered the lymphatic system. When cancer cells move into these systems, which circulate throughout the body, it’s much more likely that the cancer will spread to a new part of the body.

   Mucinous tumors: These tumors spread quickly and exist in pools of excess mucus. In signet-ring tumor cells, it’s mucus that pushes the cell’s nucleus over to one side and gives the cell its distinctive shape. While all cancers learn how to better hide over time, this is especially true of solid tumors like these. A type of cancer vaccine in trials now uses a patient’s dendritic cells, which are blood cells that act like messengers in the immune system: The blood cells are trained in a lab to activate other cancer-fighting cells, then reintroduced into the patient.

7. Photo

   

   Source: National Cancer Institute CreditIllustration by Cristiana Couciero

8. Photo

   

   Source: National Cancer Institute CreditIllustration by Cristiana Couciero

9. Photo

   

   LYMPHATIC SYSTEM

   CASES: 81,080 • DEATHS: 21,270 • SURVIVAL: 73%

   Lymphoma is any cancer that begins somewhere in the lymphatic system — often the lymph nodes, which are little oval organs that act as filters for invasive particles like viruses, bacteria and cancer. Connecting the nodes are lymphatic vessels, which are like veins but, instead of carrying blood, circulate lymph, a fluid filled with white blood cells called lymphocytes. The lymphatic system collects fluids, wastes and invasive particles from the parts of our body outside the bloodstream; lymphomas weaken the immune system, and increase the odds of a bad infection. The interconnected whole-body systems of lymph and blood are also the pathways cancer uses to spread during metastasis. Our lymph system is incredibly complicated, and so are lymphomas: There are dozens and dozens of categories and subcategories, each quite different from the next.

   Hodgkin lymphomas: These begin in lymphocytes. As many as 95 percent of all patients with Hodgkin have a form called classical Hodgkin, with enlarged, cancerous lymphocytes called Reed-Sternberg cells; the other 5 percent have cells that look like popcorn and are called popcorn cells. Most cancer cells are sensitive to DNA damage, which is how most chemotherapy works: by using agents that attack the bonds that form DNA’s double helix, breaking the strands, stopping the cancer cells from multiplying and killing them. The first F.D.A.-approved chemo­therapy was a nitrogen mustard (similar to mustard gas) for Hodgkin lymphoma, in 1949.

   Non-Hodgkin lymphomas: The remaining forms of lymphoma are far more common and can be divided into many more subgroups, some of which are considerably more aggressive than Hodgkin lymphomas. If the cells appear grouped together in structures called follicles, it’s a follicular type; or it might be spread out, making it a diffuse type; low-grade or indolent lymphomas grow slowly; high-grade or aggressive lymphomas grow quickly. A promising new form of treatment for lymphomas takes a patient’s T cells, a type of immune cell found in blood, and genetically engineers them in the lab to produce special receptors on their surface called chimeric antigen receptors (CARs). These CAR-T cells can recognize proteins on tumor cells that had masked the cancer from the patient’s immune system. The underlying principle of a lot of immunotherapies is similar: to unmask the cancer, so the immune system will attack it.

10. Photo

    

    BLADDER

    CASES: 76,960 • DEATHS: 16,390 • SURVIVAL: 78%

    Blood in urine is by far the most common symptom of bladder cancer, and usually the first to be detected. It occurs in about eight out of 10 people who have bladder cancer, which is far more common in men, especially white men. Bladder cancer often spreads, even after treatment, to different parts of the urinary tract, including the linings of the kidney, ureter and urethra. Researchers are finding, though, that there is a window of opportunity between treatments. While the cancer is developing resistance to previous treatments, it’s espe­cially vulnerable to new ones. One gene therapy uses modified viruses to infect bladder-cancer cells, marking them with a hormone that sends a chemical signal to the immune system to attack them.

    Urethral: About 95 percent of bladder cancers develop in the bladder’s innermost lining, called the urothelium. These cells bunch and stretch, depending on whether or not the bladder is empty or full. In so doing, they come into contact with urine and, more important, chemicals carried in the urine that may cause cancer. (Chemicals from tobacco smoke are a possible cause of bladder cancer, as are arsenic and diesel exhaust.)

    Non-muscle invasive: Also called superficial or early bladder cancer, it can appear as small growths that look like cauliflower in the lining of the organ. The cancer might later move from its superficial or early designation to become invasive, at which point it has a high chance of metastasizing.

11. Photo

    

    Source: American Cancer Society. Chart estimates based on United States population in 2016.CreditIllustration by Cristiana Couciero

12. Photo

    

    SKIN (MELANOMA)

    CASES: 76,380 • DEATHS: 10,130 • SURVIVAL: 92%

    Skin cancer is the most commonly diagnosed form of cancer in the United States, but the most common types — basal-cell and squamous-cell skin cancer (also called nonmelanoma skin cancer) are found so early and so often that they are not required to be reported to cancer registries in North America. The best way to detect skin cancer early is to recognize new or changing skin growths, particularly those that look different from other moles. Use the ABCDE rules: A is for asymmetry (one half of the mole does not match the other half); B is for border irregularity (ragged, notched, or blurred edges); C is for color (not uniform, with shades of tan, brown, or black in one mole); D is for diameter greater than 6 milli­meters (about the size of a pencil eraser); and E is for evolution (in other words, change). Mela­nomas represent about 1 percent of all skin-cancer cases but nearly all skin-cancer deaths, because they grow and metastasize so much faster than other forms of skin cancer.

    Superficial spreading: The most common form of melanoma (about 70 percent of all cases), it first appears as a flat or slightly raised discolored patch that has irregular borders and is somewhat asymmetrical in form. It can begin in what was previously a benign mole.

    Lentigo maligna: Similar to superficial spreading melanoma, it stays close to the skin surface and shows discoloration, but is most common in the elderly and chronically sun-exposed (it’s the most common form of melanoma in Hawaii).

    Acral lentiginous: Usually appearing as a black or brown discoloration under the nails or on the soles of the feet or palms of the hands, it is the most common form of melanoma in African-Americans and Asians.

    Nodular: A very aggressive melanoma, it is usually invasive at the time of diagnosis.

13. Photo

    

    THYROID

    CASES: 64,300 • DEATHS: 1,980 • SURVIVAL: 98%

    Thyroid cancers are among the most treatable cancers. In some cases, they’re diagnosed after a lump in the neck is found; in others, when a patient feels tightness in the throat or hoarseness or has a hard time breathing or swallowing. Only about 5 percent of thyroid cancers grow aggressively and present a risk of spreading to other organs. Many thyroid tumors are so slow-growing that earlier this year, an international panel of pathologists decided that a whole category of thyroid tumors (about one-sixth of the 64,300 cases cited above) would no longer be considered cancer. Most thyroid cancers do not respond well to chemotherapy, but some newer targeted drugs show incredible promise. One class, known as kinase inhibitors, helps block certain enzymes common to thyroid cancer, and also blocks the growth of blood vessels. (Cancer tumors often survive by getting the body to form new blood vessels, a process called angiogenesis.)

    Differentiated: Nearly 90 percent of thyroid cancer cases involve differentiated thyroid cancers (D.T.C.), in which the cancer mutation doesn’t look all that different from a typical thyroid cell. But D.T.C. is itself divided into four groups. A subset of one of them, the encapsulated follicular variant of papillary thyroid cancer, is the kind that was downgraded this year. It is more common in women and younger people and is fairly treatable.

    Medullary thyroid: This sometimes comes from having an inherited abnormality in a specific gene called RET. Patients with the abnormal RET gene that causes medullary thyroid cancer often have their thyroid removed as a preventive step.

14. Photo

    

    KIDNEY

    CASES: 62,700 • DEATHS: 14,240 • SURVIVAL: 74%

    Kidneys filter blood, transforming excess water, salt and other waste into urine. Blood enters them through the renal arteries; urine exits through ureters at the renal pelvis. The renal cells lining the tubes in and out of the kidney are where nearly all kidney cancers first appear. Kidney cancer has long been resistant to chemotherapy, but researchers are finding more success with targeted drug treatments (called adjuvant therapy) delivered after surgery, which attack the genetic mutations underlying a tumor’s growth. Until recently most pathology reports for kidney cancer listed it simply as renal cell carcinoma (R.C.C.), but now they more often break it into subcategories.

    Clear-cell: Also known as conventional R.C.C., it accounts for nearly 75 percent of all cases. Like many other kidney cancers, it’s difficult to diagnose at an early stage, but a few signs include blood in urine or a lump in the abdomen.

    Papillary R.C.C.: This category is divided further, into Type I (5 percent of all cases) and Type II (10 percent). Type I is usually hereditary, meaning a gene — in this case one called MET — passed down from a parent can greatly increase the risk of this cancer. These inherited genetics appear in germline cells, or reproductive cells, which are different from adult cells, also called somatic cells. About 85 to 90 percent of all cancers come from sporadic mutations in somatic cells, and the rest are related to inherited mutations in germline cells. When researchers talk about genetically sequencing cancer, they are talking about sequencing somatic cells. But some cancers, like Type II Papillary R.C.C., carry distinct inherited risks, which germline cell sequencing can reveal.

15. Photo

    

    BLOOD (LEUKEMIA)

    CASES: 60,140 • DEATHS: 24,400 • SURVIVAL: 60%

    Most types of leukemia start in immature blood stem cells, which are found in bone marrow. Stem cells develop into different types of cells that have different jobs. Blood stem cells develop into either lymphoid stem cells or myeloid stem cells. Lymphoid stem cells develop into lymphocytes, a type of white blood cell; myeloid stem cells sometimes develop into bone-marrow-based blood cells, like platelets. Cancer has stem cells, too, which were first discovered in acute myeloid leukemia, in 1994. Leukemia is either acute or chronic. Acute is fast-growing; chronic is not. Many types of chronic leukemia can be controlled and lived with for years and even decades — something also increasingly true of many other cancers. More people are living with cancer today than ever before in history.

    Chronic lymphocytic: A cancer of the lymphocytes, which are white blood cells that fight infections, it’s the most common form of leukemia in the United States. Relapsed chronic lymphocytic leukemia (C.L.L.) is harder to treat: The tumors are more likely to be resistant to previous treatments (chemotherapy in particular). One new class of drugs targets a specific genetic mutation associated with chemoresistance to slow the cancer’s spread.

    Acute lymphoblastic: This is the most common type of leukemia in young children. The standard treatment for acute lymphoblastic leu­kemia (A.L.L.) is usually chemotherapy, and the survival rate tends to be much higher in children than adults (85 percent versus 50 percent). One challenge of all leukemias — all cancers, really — is knowing just how many cancerous cells remain in the body after treatment, especially since even a few can give rise to a relapse. A polymerase chain reaction (P.C.R.) test can identify trace amounts of cancer cells based on the cancer’s gene mutations — its genetic fingerprint. Cancer’s ability to mutate is what makes it a tricky, ever-changing foe; but the more we understand these genetics, the more we can take advantage of them.