Month: May 2021

In the US, breast cancer is the most commonly diagnosed cancer in women, and the second leading cause of cancer-related deaths. Each year, an estimated 270,000 women — and a far smaller number of men — are diagnosed with it. When caught in early stages, it’s usually highly treatable.

A promising new form of targeted treatment may expand options available to some women with early-stage breast cancer linked to specific genetic glitches. (Early-stage cancers have not spread to distant organs or tissues in the body.)

The BRCA gene: What does it do?

You may have heard the term BRCA (BReast CAncer) genes, which refers to BRCA1 and BRCA2genes. Normally, BRCA genes help repair damage to our DNA (genetic code) that occurs regularly in cells throughout the human body.

Inherited BRCA mutations are abnormal changes in these genes that are passed on from a parent to a child. When a person has a BRCA mutation, their body cannot repair routine DNA damage to cells as easily. This accumulating damage to cells may help pave a path leading to cancer. Having a BRCA1 or BRCA2 mutation — or both — puts a person at higher risk for cancer of the breast, ovaries, prostate, or pancreas; or for melanoma. A person’s risk for breast cancer can also be affected by other gene mutations and other factors.

Overall, just 3% to 5% of all women with breast cancer have mutations in BRCAgenes. However, BRCA mutations occur more often in certain groups of people, such as those with triple negative breast cancer (TNBC), Ashkenazi Jewish ancestry, a strong family history of breast and/or ovarian cancer, and younger women with breast cancer.

Inherited BRCA mutations and breast cancer types

Certain types of breast cancer are commonly found in women with BRCA gene mutations.

• Estrogen receptor-positive, HER2-negative cancer: Women with a BRCA2 mutation usually develop ER+/HER2- breast cancer — that is, cancer cells that are fueled by the hormone estrogen but not by a protein known as HER2 (human epidermal growth factor 2).
• Triple negative breast cancer: Women with a BRCA1 mutation tend to develop triple negative breast cancer (ER-/PR-/HER2-) — that is, cancer cells that aren’t fueled by the hormones estrogen and progesterone, or by HER2.

Knowing what encourages different types of breast cancer to grow helps scientists develop new treatments, and helps doctors choose available treatments to slow or stop tumor growth. Often this involves a combination of treatments.

A new medicine aimed at early-stage BRCA-related breast cancers

The OlympiA trial enrolled women with early-stage breast cancer and inherited BRCA1/BRCA2 mutations. All were at high risk for breast cancer recurrence despite standard treatments.

Study participants had received standard therapies for breast cancer:

• surgery (a mastectomy or lumpectomy)
• chemotherapy (given either before or after surgery)
• possibly radiation
• possibly hormone-blocking treatment known as endocrine therapy.

They were randomly assigned to take pills twice a day containing olaparib or a placebo (sugar pills) for one year.

Olaparib belongs to a class of medicines called PARP inhibitors. PARP (poly adenosine diphosphate-ribose polymerase) is an enzyme that normally helps repair DNA damage. Blocking this enzyme in BRCA-mutated cancer cells causes the cells to die from increased DNA damage.

Results from this study were published in the New England Journal of Medicine. Women who received olaparib were less likely to have breast cancer recur or metastasize (spread to distant organs or tissues) than women taking placebo. Follow-up at an average of two and a half years showed that slightly more than 85% of women who had received olaparib were alive and did not have a cancer recurrence, or a new second cancer, compared with 77% of women treated with placebo.

Further, the researchers estimated that at three years:

• The likelihood that cancer would not spread to distant organs or tissues was nearly 88% with olaparib, compared to 80% with placebo.
• The likelihood of survival was 92% for the olaparib-treated group and 88% for the placebo group.

The side effects of olaparib include low white cell count, low red cell count, and tiredness. The chances of developing these were low.

The bottom line

Olaparib is already approved by the FDA to treat BRCA-related cancers of the ovaries, pancreas, or prostate, and metastatic breast cancer. FDA approval for early-stage breast cancer that is BRCA-related is expected soon based on this study. These findings suggest taking olaparib for a year after completing standard treatment could be a good option for women who have early-stage breast cancer and an inherited BRCA gene mutation who are at high risk for cancer recurrence and, possibly, its spread.

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Last week, the FDA authorized the Pfizer/BioNTech COVID vaccine for children ages 5 to 11. After conducting their own review, the CDC now recommends this vaccine for children in this age range, who can begin receiving their first dose within the week.

While many families have been eagerly awaiting the opportunity for their children to be immunized, others are hesitant. And most parents have questions about how COVID-19 affects younger children, vaccine safety in this age range, and whether the benefits outweigh potential risks. As a pediatric infectious disease specialist, I hear certain questions crop up repeatedly. Here’s what we know so far.

How does COVID-19 affect children in this age range?

While children continue to be much less likely than adults — especially adults 65 and older — to get severely ill from COVID-19, some children do get very sick. Thousands of children 5 to 11 have been hospitalized or need ICU-level support to recover from this infection. Almost 150 children in this age range have died from COVID-19. Additionally, over 5,000 cases of a serious inflammatory condition known as MIS-C that can follow COVID-19 infection have been reported. The majority of cases of MIS-C have occurred in children in this age range.

How has the Delta strain of the virus affected children?

The Delta strain of the virus that causes COVID spreads easily, particularly among people who haven’t received the vaccine. Children ages 5 to 11 remain more susceptible to infection, given their ineligibility to be vaccinated. In fact, more than one in five new cases recorded over the past two months while Delta infections surged in the US occurred in this age group, according to weekly reports from the American Academy of Pediatrics and the Children’s Hospital Association.

Can children spread the virus to others?

Several detailed reports describing outbreaks associated with settings such as summer camps, daycares, and schools, and those tracing transmission of COVID-19 within households, clearly demonstrate that children can spread this virus and infect others with whom they come into close contact.

Which COVID vaccines and doses are authorized for children ages 5 to 11?

Pfizer/BioNTech is the first COVID vaccine authorized by the FDA for this age group, based on results from a randomized controlled trial evaluating safety and immune responses. A separate trial launched by Moderna is being considered separately.

In a small number of children, the Pfizer/BioNTech trial compared three doses:

• 30 micrograms (the dose adults receive)
• 20 micrograms
• 10 micrograms.

This part of the trial showed that 10 micrograms, the smallest dose, resulted in fewer side effects while still generating robust immune responses similar to responses achieved with higher doses.

In the next part of the trial, more than 2,200 children ages 5 to 11 were randomly assigned to receive either a 10-microgram dose of the vaccine (two-thirds of participants) or a placebo dose (one-third of participants). All received two shots, spaced three weeks apart.

Those given the vaccine had similar immune responses as 16-to-25-year-olds who had received the full-dose series of two shots.

When Pfizer/BioNTech submitted data to the FDA, there were not many cases of symptomatic COVID-19 infections in trial participants. Out of 19 documented cases, most had received the placebo shots. Estimates suggest the efficacy rate of the vaccine is 90%. (Efficacy measures how much a vaccine reduces infection in a controlled trial.) Tests confirmed that the Delta viral strain had caused the infections.

What do we know about side effects for children this age?

Most children had no side effects other than pain at the injection site. Those who did have side effects most commonly experienced fatigue, headaches, and/or muscle aches after the second dose rather than the first dose. For example, only 6% of children had fever after the second vaccine dose. There were no cases of severe allergic reaction to the vaccine.

What is not yet known?

In very rare instances, the Pfizer/BioNTech COVID-19 vaccine is linked to myocarditis, which is an inflammation of the heart. When this occurs, it is mostly seen in young males following their second dose of an mRNA vaccine (Pfizer/BioNTech or Moderna). Most cases are mild, and children show no signs of long-term injury to the heart.

Among the 5-to-11-year-olds who received the Pfizer vaccine during the trial, there were no cases of myocarditis. However, this side effect is very rare and might not be noted until the number of children receiving the vaccine is much higher. The FDA and Pfizer/BioNTech will continue to closely monitor this age group for any occurrence of this rare side effect.

Can children get vaccinated against COVID-19 and influenza at the same time?

Yes. Children and adults can safely get both vaccines at the same time. The CDC urges everyone to get flu shots to help stay healthy during this flu season.

A randomized, controlled trial in the UK evaluated adults who received a flu shot or placebo shot in one arm and their second dose of the Pfizer/BioNTech vaccine in the other arm. The researchers reported in Preprints with The Lancet that side effects and immune responses were similar, whether the flu shot or a placebo shot was given at the same time as the COVID vaccine.

What other steps can parents take to protect children against COVID-19?

Parents should remember that an individual is not fully immunized and protected by the vaccine until 14 days after the second dose of the Pfizer vaccine. Masks are recommended for anyone who is unvaccinated, or not fully immunized, when indoors with people outside of their household. If rates of COVID-19 are high where you live, masks may be recommended indoors for vaccinated individuals as well.

Parents can continue to encourage other simple habits that help prevent colds, flu, and COVID-19, such as washing hands often, coughing or sneezing into an elbow, throwing away used tissues quickly, and avoiding crowded places and people who are ill when possible.