278 ‒ Breast cancer: how to catch, treat, and survive breast cancer | Harold Burstein, M.D., Ph.D.

KEYPOINTS

• 01

  Breast cancer is common, but most women are now cured

  Harold Burstein, a Dana-Farber breast oncologist, gives a US lifetime risk of about 1 in 8 (12–13%). There are roughly 250,000–300,000 invasive cases a year (he first says about 275,000), plus another 50,000–60,000 cases of DCIS, and about 38,000 deaths. Assuming a steady state, about 80–85% of women are cured, while 15–18% remain at risk of recurrence and death. Outcomes depend on both stage and subtype.

• 02

  Three subtypes drive treatment

  Estrogen-receptor-positive, HER2-negative tumours make up 70–75% or more. They are the type most often found on mammograms, peak around age 65 and, size for size, usually have the best prognosis. Triple-negative cancers (ER, PR and HER2 negative) are about 10–15%, skew younger and are more aggressive. HER2-positive tumours were once very aggressive but now have some of the best treatment results.

• 03

  Most risk factors move individual risk only a little

  Early first period, late menopause, hormone therapy, fewer pregnancies and less breastfeeding all extend estrogen exposure and may raise risk 25–30%. Burstein says that only moves an individual from about 12% to about 15%. Postmenopausal women with denser breast tissue are at slightly higher risk, and not just because density hides tumours. He calls obesity a relatively weak risk factor, and smoking is not a major one.

• 04

  DCIS is a precancer, like a colon polyp

  Ductal carcinoma in situ is cells building up inside a duct without invading the surrounding tissue. Seventy years ago it showed up as a lump, but today it is found on mammograms. In about 15–20% of excisions, a small invasive cancer turns up, so the diagnosis is upgraded. In the NSABP B-17 trial, about 25–30% of women treated with lumpectomy alone had a recurrence or new breast cancer within 10 years, and radiation cut that roughly in half. B-24 added tamoxifen. Burstein thinks the baseline risk for today's mammogram-detected DCIS is much lower.

• 05

  Radiation after DCIS is a trade-off in risk

  For healthy women up to about 65–70, radiation after lumpectomy is standard. It lowers the risk in that breast to something like 1–2% with three to four weeks of treatment. Recurrence risk without radiation ranges from about 5–10% for low-risk lesions to 20–25% for higher-risk ones. Ongoing trials ask which low-risk women can safely skip it.

• 06

  LCIS signals higher risk rather than being a precursor that must be removed

  Lobular carcinoma in situ and atypical hyperplasia raise the risk of future cancer by roughly 0.5–1% a year and warrant monitoring. In the NSABP P1 prevention trial, which enrolled many women with LCIS, tamoxifen cut breast cancer diagnoses from about 13 to 5–6 per 1,000 women per year. However, it did not improve survival, partly because it prevents the most treatable tumours.

• 07

  Stage, nodes and biology together predict cure

  Burstein's ballpark 10-year cancer-free survival figures are about 90% or more for stage 1, 75–80% for stage 2 and 65–75% for stage 3. Peter cites 90–95% for tumours of 2 cm or smaller without lymph-node involvement. Risk rises steadily with size, with each additional lymph node, and with tumour grade, Ki-67 and receptor status.

• 08

  Genomic tests now spare many women chemotherapy

  In 1999 the NCI said essentially every woman with a 1 cm cancer needed chemotherapy. Today, ER-positive tumours are scored with tests such as the Oncotype DX recurrence score or MammaPrint, which show that most low-scoring patients gain little from chemotherapy. Anti-estrogen therapy is advised for nearly all ER-positive patients, longer for high-risk cases, and oral CDK4/6 inhibitors are now added for very high-risk tumours.

• 09

  Screening plus better drugs each account for about half the mortality decline

  Breast cancer mortality has fallen by about half over 30–40 years. Burstein credits roughly half of that to early detection and half to effective drug therapy, notably trastuzumab (Herceptin) for HER2-positive disease, with data emerging in 2005. Neoadjuvant therapy, meaning drugs before surgery, is increasingly used for larger tumours, and the tumour's response guides prognosis and later treatment.

• 10

  Hereditary mutations explain only about 8–10% of cases

  BRCA1 and BRCA2 account for about half of hereditary cases, and PALB2, CHEK2 (also linked to colon cancer) and ATM for most of the rest. Clinical panels now test up to about 100 genes. Burstein doesn't rely on consumer tests like 23andMe for clinical decisions. Carriers may consider preventive mastectomy, ovary removal once childbearing is done (there is no good ovarian screening), or intensive screening: an annual MRI and an annual mammogram, staggered six months apart.