Washington Manual of Medical Therapeutics
General Principles
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Background
Cancer is one of the leading causes of mortality both worldwide and in the US, accounting for approximately 608,000 deaths in the US in 2020.1 The most common malignancies in the US are lung cancer, prostate cancer, breast cancer, and colon cancer (Table 22-1). Cancer death rates have declined by an estimated 29% over the past 3 decades owing to better uptake of screening strategies, advances in drug development, and the availability of better supportive care. Improved understanding of the molecular pathways operative in cancer cells and their complex interactions with the immune system and the tumor microenvironment has also led to the development of targeted agents, immunotherapies, and personalized treatment approaches associated with significant clinical benefit.
| Sites | New Cases | Deaths | ||
| Both Sexes | Male | Female | Total | |
| Lung | 228,820 | 116,300 | 112,520 | 135,720 |
| Prostate | 191,930 | 191,930 | – | 33,330 |
| Breast | 279,100 | 2,620 | 276,480 | 42,690 |
| Colon/rectal | 147,950 | 78,300 | 69,650 | 53,200 |
Risk Factors
- Tobacco use is the most common cause of cancer and is associated with lung, head and neck, esophageal, gastric, pancreatic, kidney, and bladder cancers.
- Diet, obesity, inactivity, and alcohol abuse have been associated with increased risk of developing certain cancers.
- Chronic inflammatory states such as ulcerative colitis and infections including HIV, hepatitis, Epstein–Barr virus (EBV), human papillomavirus (HPV) and Helicobacter pylori are associated with increased cancer risk.
- Numerous familial cancer syndromes have been described and have important implications for cancer risk and screening (Table 22-2).
- Prior exposure to cytotoxic chemotherapy or radiation therapy is associated with an increased risk of secondary cancers. For example, exposure to alkylating agents or topoisomerase II inhibitors increases the risk of treatment-related leukemia, and exposure to radiation therapy increases risk for cancers such as breast cancer, angiosarcoma, and osteosarcoma.
| Syndrome | Defect | Associated Cancer Type |
| Ataxia–telangiectasia | ATM | Multiple; predominantly leukemia and lymphoma |
| Birt–Hogg–Dube | BHD | Chromophobe RCC |
| Bloom syndrome | BLM | Multiple |
| Cowden syndrome | PTEN | Multiple; predominantly breast, thyroid, RCC, endometrial |
| Familial adenomatous polyposis | APC | Colorectal, desmoid |
| Fanconi anemia | DNA repair complex | Multiple; predominantly MDS and AML |
| Hereditary breast–ovarian cancer | BRCA1 and BRCA2 | Multiple; predominantly breast, ovarian |
| Hereditary diffuse gastric cancer | CDH1 | Gastric, lobular breast cancer |
| Hereditary leiomyomatosis and RCC | FH | Papillary RCC |
| Lynch syndrome (HNPCC) | Mismatch repair | Multiple; predominantly colorectal |
| Hereditary papillary RCC | MET | Papillary RCC |
| Juvenile polyposis syndrome | MADH4 (SMAD4), BMPR1A | Digestive tract and pancreas |
| Li-Fraumeni syndrome | TP53 | Multiple |
| MEN type 1 | MEN1 | Islet cell tumors |
| MEN type 2 | RET | Medullary thyroid cancer |
| Neurofibromatosis type 1 | NF1 | MPNST, glioma |
| Neurofibromatosis type 2 | NF2 | Meningioma, glioma, schwannoma |
| Nijmegen breakage syndrome | NBS1 | Predominantly lymphoma |
| Peutz–Jeghers syndrome | LKB1 (STK11) | Multiple; predominantly breast, GI, pancreas |
| Retinoblastoma, hereditary | RB | Retinoblastoma, primitive neuroectodermal tumor |
| Rothmund–Thomson syndrome | RECQL4 | Osteosarcoma |
| Tuberous sclerosis (TS) | TSC1, TSC2 | RCC, giant cell astrocytoma |
| von Hippel-Lindau | VHL | Clear cell RCC |
| Xeroderma pigmentosum | Nucleotide excision repair | Multiple, cutaneous |
AML, acute myeloid leukemia; GI, gastrointestinal; HNPCC, hereditary nonpolyposis colorectal cancer; MDS, myelodysplastic syndrome; MEN, multiple endocrine neoplasia; MPNST, malignant peripheral nerve sheath tumor; RCC, renal cell carcinoma.
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Background
Cancer is one of the leading causes of mortality both worldwide and in the US, accounting for approximately 608,000 deaths in the US in 2020.1 The most common malignancies in the US are lung cancer, prostate cancer, breast cancer, and colon cancer (Table 22-1). Cancer death rates have declined by an estimated 29% over the past 3 decades owing to better uptake of screening strategies, advances in drug development, and the availability of better supportive care. Improved understanding of the molecular pathways operative in cancer cells and their complex interactions with the immune system and the tumor microenvironment has also led to the development of targeted agents, immunotherapies, and personalized treatment approaches associated with significant clinical benefit.
| Sites | New Cases | Deaths | ||
| Both Sexes | Male | Female | Total | |
| Lung | 228,820 | 116,300 | 112,520 | 135,720 |
| Prostate | 191,930 | 191,930 | – | 33,330 |
| Breast | 279,100 | 2,620 | 276,480 | 42,690 |
| Colon/rectal | 147,950 | 78,300 | 69,650 | 53,200 |
Risk Factors
- Tobacco use is the most common cause of cancer and is associated with lung, head and neck, esophageal, gastric, pancreatic, kidney, and bladder cancers.
- Diet, obesity, inactivity, and alcohol abuse have been associated with increased risk of developing certain cancers.
- Chronic inflammatory states such as ulcerative colitis and infections including HIV, hepatitis, Epstein–Barr virus (EBV), human papillomavirus (HPV) and Helicobacter pylori are associated with increased cancer risk.
- Numerous familial cancer syndromes have been described and have important implications for cancer risk and screening (Table 22-2).
- Prior exposure to cytotoxic chemotherapy or radiation therapy is associated with an increased risk of secondary cancers. For example, exposure to alkylating agents or topoisomerase II inhibitors increases the risk of treatment-related leukemia, and exposure to radiation therapy increases risk for cancers such as breast cancer, angiosarcoma, and osteosarcoma.
| Syndrome | Defect | Associated Cancer Type |
| Ataxia–telangiectasia | ATM | Multiple; predominantly leukemia and lymphoma |
| Birt–Hogg–Dube | BHD | Chromophobe RCC |
| Bloom syndrome | BLM | Multiple |
| Cowden syndrome | PTEN | Multiple; predominantly breast, thyroid, RCC, endometrial |
| Familial adenomatous polyposis | APC | Colorectal, desmoid |
| Fanconi anemia | DNA repair complex | Multiple; predominantly MDS and AML |
| Hereditary breast–ovarian cancer | BRCA1 and BRCA2 | Multiple; predominantly breast, ovarian |
| Hereditary diffuse gastric cancer | CDH1 | Gastric, lobular breast cancer |
| Hereditary leiomyomatosis and RCC | FH | Papillary RCC |
| Lynch syndrome (HNPCC) | Mismatch repair | Multiple; predominantly colorectal |
| Hereditary papillary RCC | MET | Papillary RCC |
| Juvenile polyposis syndrome | MADH4 (SMAD4), BMPR1A | Digestive tract and pancreas |
| Li-Fraumeni syndrome | TP53 | Multiple |
| MEN type 1 | MEN1 | Islet cell tumors |
| MEN type 2 | RET | Medullary thyroid cancer |
| Neurofibromatosis type 1 | NF1 | MPNST, glioma |
| Neurofibromatosis type 2 | NF2 | Meningioma, glioma, schwannoma |
| Nijmegen breakage syndrome | NBS1 | Predominantly lymphoma |
| Peutz–Jeghers syndrome | LKB1 (STK11) | Multiple; predominantly breast, GI, pancreas |
| Retinoblastoma, hereditary | RB | Retinoblastoma, primitive neuroectodermal tumor |
| Rothmund–Thomson syndrome | RECQL4 | Osteosarcoma |
| Tuberous sclerosis (TS) | TSC1, TSC2 | RCC, giant cell astrocytoma |
| von Hippel-Lindau | VHL | Clear cell RCC |
| Xeroderma pigmentosum | Nucleotide excision repair | Multiple, cutaneous |
AML, acute myeloid leukemia; GI, gastrointestinal; HNPCC, hereditary nonpolyposis colorectal cancer; MDS, myelodysplastic syndrome; MEN, multiple endocrine neoplasia; MPNST, malignant peripheral nerve sheath tumor; RCC, renal cell carcinoma.
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