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Why do most breast cancers occur in women?

Why do most breast cancers occur in women?


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According to Korde et al. (2010):

Male breast cancer accounts for less than 1% of all cancers in men and less than 1% of breast cancers.

This raises the question: Why do most breast cancers occur in women?

Two plausible explanations I can think of:

  • A male is less likely to get breast cancer for anatomical reasons (such as a smaller quantity of breast tissue, or breast tissue that is less susceptible to cancer),

  • Women have higher significantly levels of estrogen, which is linked to mutations that cause breast cancer (see Cavalieria et al. (2006)).

Although, I have no evidence to suggest that either of these is predominant factor.


Yes, this is mostly about estrogen. Most breast cancers rely on endogenous estrogen to sustain proliferation.

Some general reading: Cancer Medicine, Chapter 18

More in-depth reading: Endogenous Hormones as a Major Factor in Human Cancer

Requested summary of mentioned readings:

First of all, there is an established link between breast cancer cell proliferation and concentration of estrogens and progesterone, which is logical, because normal breast cells divide in response to those hormones (e.g. puberty, pregnancy, even luteal phase of the menstrual cycle). Secondly, the incidence of breast cancer in women correlates with major changes in their hormonal profile - girls and elderly women (i.e. women with lower levels of sex hormones) don't get breast cancer.

Many factors, that influence the risk of developing breast cancer are in fact tightly connected to the hormones' levels. For example - early age of menarche (or, more importantly, first ovulation, because physical activity at young age disturbs ovulation AND is protective against breast cancer) and Hormone Replacement Therapy raise the risk, early age of first full-term pregnancy or any form of artificial menopause (such as preventive oophorectomy for women with mutations in BRCA1 or 2) reduce the risk.

The first table from the book chapter lists known risk and preventive factors. The review article explains the same ideas, but connects them to other types of cancer (e.g. ovarian cancer) and suggests mechanisms, which might be the cause of those risk changes.


For two reasons: Women are

  1. exposed to estrogen,¹ and
  2. the lobules in a woman's breast go through 4 stages:

Type 1: prepubescent & Type 2: pubescent

Type 3: reproductive & Type 4: lactation lobules²

The sooner a woman progresses to Type 3 and Type 4 lobules, the lower her risk of cancer. An interruption of the progression from Type 1 to Type 4 lobules (such as with a late-term miscarriage or induced abortion) increases the risk of cancer, as cancer generally arises in Type 1 and Type 2 lobules.³

References

  1. Miller, Katherine. Estrogen and DNA damage: The silent source of breast cancer? J Natl Cancer Inst 2003: 95:100-102.
  2. Schwartz, Shires, Spencer, Principles of Surgery (McGraw Hill) Russo J, Tay LK, Russo IH. Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Res & Treatment 1982;2:5-73.
  3. Daling JR, Malone DE, Voigt LF, White E, Weiss NS. Risk of breast cancer among young women: relationship to induced abortion. J Natl Cancer Inst 1994;86:1584-92.

Breast cancer statistics

Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. There were over 2 million new cases in 2018. The top 25 countries with the highest rates of breast cancer in 2018 are given in the table below.

The Continuous Update Project Panel judged that there was strong evidence that consumption of alcoholic drinks, greater birthweight and adult attained height are causes of premenopausal breast cancer. The panel also judged that there is strong evidence that vigorous physical activity and greater body fatness protect against premenopausal breast cancer (more information about this unusual finding on greater body fatness can be found in Appendix 2 of Body fatness and weight gain (PDF)).

The Panel judged that there was strong evidence that consumption of alcoholic drinks, greater body fatness throughout adulthood, adult weight gain and adult attained height are causes of postmenopausal breast cancer. The Panel also judged there is strong evidence that physical activity (including vigorous physical activity) and greater body fatness in young adulthood protect against postmenopausal breast cancer (more information about this unusual finding on greater body fatness in young adulthood can be found in Appendix 2 of Body fatness and weight gain (PDF)).

In addition, the Panel judged there was strong evidence that lactation protects against breast cancer (unspecified menopausal status).

We also fund research on breast cancer through our regular grant programme. Read the findings here.

Age-standardised rates are used in the tables. This is a summary measure of the rate of disease that a population would have if it had a standard age structure. Standardisation is necessary when comparing populations that differ with respect to age because age has a powerful influence on the risk of dying from cancer.


Causes Of Breast Cancer: How Did This Happen?

When you’re told that you have breast cancer, it’s natural to wonder what may have caused the disease. But no one knows the exact causes of breast cancer. Doctors seldom know why one woman develops breast cancer and another doesn’t, and most women who have breast cancer will never be able to pinpoint an exact cause. What we do know is that breast cancer is always caused by damage to a cell’s DNA.


Kinds of Breast Cancer

The most common kinds of breast cancer are&mdash

  • Invasive ductal carcinoma. The cancer cells grow outside the ducts into other parts of the breast tissue. Invasive cancer cells can also spread, or metastasize, to other parts of the body.
  • Invasive lobular carcinoma. Cancer cells spread from the lobules to the breast tissues that are close by. These invasive cancer cells can also spread to other parts of the body.

There are several other less common kinds of breast cancer, such as Paget&rsquos disease, external icon medullary, mucinous, and inflammatory breast cancer. external icon

Ductal carcinoma in situ (DCIS) is a breast disease that may lead to breast cancer. The cancer cells are only in the lining of the ducts, and have not spread to other tissues in the breast.


Triple negative breast cancer (TNBC)

Prevalence rates of triple negative breast cancer (TNBC) differ by race and ethnicity.

  • Estrogen receptor-negative (ER-negative)
  • Progesterone receptor-negative (PR-negative)
  • HER2-negative

TNBC is more common among Black and African American women than among women of other ethnicities [326,328-332]. TNBC may also be more common among Hispanic women compared to white and non-Hispanic white women [333-335].

TNBC is often aggressive. TNBC is more likely than estrogen receptor-positive (ER-positive) breast cancers to recur, at least within the first 5 years after diagnosis [326,336-338].

Possible reasons for differences in rates of TNBC

Although the reasons for racial and ethnic differences in rates of TNBC aren’t clear, some lifestyle factors may play a role [339].

Compared to white and non-Hispanic white women, Black and African American women tend to [119-120,323,339,340-341]:

Both of these factors may be linked to an increased risk of TNBC [119-120,323,339,340-341].

Women with certain reproductive and lifestyle factors may have a lower risk of ER-positive breast cancers, but not a lower risk of ER-negative breast cancers, including TNBC [69-71,119,323,340].

Black and African American women may be more likely than white women to have protective factors that may not be linked to the risk of TNBC as much as they are linked to the risk of ER-positive cancers.

For example, Black and African American women are more likely than white and non-Hispanic white women to [119,323,340-343]:

  • Have more children
  • Be a younger age at first childbirth
  • Be overweight or obese before menopause

Although these factors are linked to a lower the risk of breast cancer, this lower risk may be limited to ER-positive breast cancers [69-71,119,323,340]. There’s even some evidence these factors may be linked to an increased risk of TNBC [69-71,119,323,340].


Differences in pathological features and subtypes within premenopausal patients: does actual age matter?

In the previously discussed studies, different age cutoffs were used to define 'young age'. In addition, the term 'young age' has often been used synonymously with 'premenopausal' in evaluations of women with breast cancer, requiring further evaluation of whether differences exist within the premenopausal population according to actual age. In 2002, Colleoni and colleagues [13] published a large analysis including 1,427 premenopausal patients who were aged ≤50 years at the time of breast cancer diagnosis. They compared the expression of ER, progesterone receptor (PgR), and ki67 and other features by young age group (<35, 35 to 40, 40 to 45 and 45 to 50 years). Significant differences were observed according to age, with aggressive features more frequently observed in tumors arising in younger patients. Similar results were also reported by the Korean Breast Cancer Society registry, which included 9,885 premenopausal breast cancer patients aged ≤50 years at diagnosis [8].

In comparing groups of very young women, however, Collins and colleagues [12] did not find significant differences in histological features or the expression of ER, PgR and HER2 between patients aged ≤30 (n = 47), 31 to 35 (n = 111) and 36 to 40 (n = 241) years at breast cancer diagnosis in a prospective study, except for a trend of higher tumor necrosis in the youngest group (32% versus 14% and 21%, P = 0.06). A retrospective analysis of 500 patients who were aged <35 years at the time of diagnosis reported the same findings, albeit a modest higher prevalence of ER-negative (31% versus 23%), and highly proliferative tumors (ki67 > 30% 59% versus 49%) among patients aged <30 and 30 to 34 years, respectively [19]. Collectively, these findings suggest that the younger the patient, the more aggressive the tumor features within the premenopausal population. Yet, it appears that differences are more subtle in women below 35 or 40 years.


What's the Best Treatment for Breast Cancer After Age 7O?

The vast majority of women diagnosed with breast cancer are older only 5% of breast cancer cases occur in women under age 40, while fully one-third of all breast cancers are diagnosed in women 70 or older.

If you're at least 70 years old, your chance of developing breast cancer in the next 20 years is about 1 in 26 yet most research around treatment, including clinical trials, focuses on women much younger. Older women have special challenges and concerns around breast cancer treatment - including whether or not to have it. Find out what you (or your mom, or an elderly relative facing breast cancer) should consider when making treatment decisions.

Breast cancer treatment is vastly improved over what it was 30 years ago, both in effectiveness, and in management of side effects. But treatment can still be very difficult - even life-threatening.

Thus, the first thing to consider is the overall health of the prospective patient.

A woman with advanced congestive heart failure, for instance, or diabetes, or an exceptionally frail woman will probably want to carefully pick and choose which treatments she has - if any. Breast cancer is generally slow-growing, especially in older women if the woman's reasonable life expectancy is 1 or 2 years, then breast cancer treatment might not make any sense at all, given its side effects.

That said, some treatments are easier on the system than others. And the bang for your buck for, say, a lumpectomy might be much greater than it is for chemotherapy. Let's examine what the data says about breast cancer treatment in older women.

Studies show
The problem is, there are few studies focusing on breast cancer treatment in women over 70, as mentioned above. Several large British trials - including one focusing on the effectiveness of aromatase inhibitors vs. tamoxifen and another examining the efficacy of chemotherapy for women over 70 with hormone-negative breast cancer - never got off the ground due to lack of participants.

Still, there's been research gathered and conclusions drawn from trials covering all ages of breast cancer survivors, trials large enough to have included a significant number of older women. The following information is based on those trials.

Surgery: yes or no?
Yes having a cancerous tumor removed will decrease risk of recurrence - although in most cases, it won't increase risk of survival.

Most breast cancers in older women are low-grade, less aggressive "early" cancers and in most cases, breast conservation surgery (lumpectomy) is every bit as effective as mastectomy. The exception would be a particularly large tumor or aggressive cancer.

But sadly, most older women have a mastectomy - whether by personal choice, or due to advice from their surgeon or a family member. In addition, fewer older women are offered reconstructive surgery. This may be due to underlying health issues that would make this type of major surgery dangerous but in some cases, the surgeon simply assumes the woman doesn't care about cosmetic results. If you're having a mastectomy and want a rebuilt breast, explore the possibility.

Radiation
Latest studies show that most older women can probably skip radiation if they so choose. Their risk of local recurrence will be higher but their survival rate will be the same, so long as they follow surgery with hormone therapy: either tamoxifen, or an aromatase inhibitor.

Why would a woman choose to skip radiation, since without it she's more likely to have a recurrence?

Because the risk of recurrence within 5 years is low across the board: 2% with radiation, 9% without. And radiation can be tough on an older woman: the daily trek to the hospital, plus the fatigue and possible pain of treatment are much less well-tolerated in older women.

The exception is women with hormone-negative cancer. Since hormone therapy isn't effective for this group, radiation is a must latest studies show that women with hormone-negative breast cancer who have a lumpectomy, but not radiation, are over 90% more likely to die of breast cancer than if theyɽ received radiation.

Luckily, brachytherapy and other "accelerated" types of radiation, some lasting as little as 5 days, are becoming more commonly available. And studies show that, for women over 70, there's no appreciable difference in results between these quicker treatments and a longer, 6-week regimen.

Chemotherapy
Researchers know that chemotherapy's effectiveness declines with age and common sense tells us that chemo's difficult side effects are more easily tolerated at age 40 than age 80 . Thus an older woman being offered a choice of chemo should think long and hard about accepting it. The Oncotype-DX test is a useful tool for any woman on the fence about chemo, but especially for an older woman trying to balance quality of life with difficult side effects.

For older women where chemotherapy is clearly indicated (e.g., the cancer has spread, is particularly aggressive, or is triple negative), a non-anthracycline type of chemo (e.g., Taxol/Taxotere + Cytoxan) is now thought to be more effective than the traditional Adriamycin + Cytoxan regimen. TC comes with far less serious side effects, and produces equally good results.

Hormone therapy
After breast-conservation surgery, taking tamoxifen or an aromatase inhibitor (Arimidex, Femara, or Aromasin) is probably the best thing an older woman can do to treat her hormone-positive breast cancer. These drugs have been proven to reduce the risk of recurrence, prolong survival - and they come with much less serious side effects than other forms of treatment.

While an AI is probably a bit more effective than tamoxifen, AIs also reduce bone mineral density. If the patient has osteoporosis, or is at risk, she might choose tamoxifen rather than an AI. She could take another drug, a bisphosphonate, to combat bone loss (Boniva, Fosamax, et. al.) but these drugs come with some pretty difficult side effects of their own.

So, bottom line, what's the best treatment for older women with breast cancer?

Depends on the woman's age and overall health. There's no magic about age 70 researchers simply have to draw a line somewhere, and that's the age they've chosen.

A healthy, active 85-year-old might choose a mastectomy and reconstruction, undergo chemotherapy and 5 years of an aromatase inhibitor, and sail through with no problems. A frail 71-year-old might struggle with even a lumpectomy and tamoxifen.

If you're an older woman facing breast cancer treatment - or if you're an older woman's caregiver - look realistically at overall health and at the effectiveness of any treatment offered, vs. its side effects. It may be a long, tough series of decisions but in the end, it's worth it to take the time to tailor treatment to your age and health - whatever those may be.


Steps you can take

While you can't stop the aging process, you can make lifestyle choices that can keep your risk as low as it can be:

These are just a few of the steps you can take. Review the links on the left side of this page for more options.

Think Pink, Live Green: A Step-by-Step Guide to Reducing Your Risk of Breast Cancer teaches you the biology of breast development and how modern life affects breast cancer risk. Download the PDF of the booklet to learn 31 risk-reducing steps you can take today.


Family history

If you have close relatives who have had breast cancer or ovarian cancer, you may have a higher risk of developing breast cancer.

However, because breast cancer is the most common cancer in women, it's possible for it to occur in more than one family member by chance.

Most cases of breast cancer do not run in families, but genes known as BRCA1 and BRCA2 can increase your risk of developing both breast and ovarian cancer. It's possible for these genes to be passed on from a parent to their child.

The genes TP53 and CHEK2, are also associated with an increased risk of breast cancer.

Speak to a GP if breast or ovarian cancer runs in your family and you're worried you may get it too. They may refer you for an NHS genetic test, which will tell you if you have inherited one of the cancer-risk genes.


Other types of cancer that occur in the breast

Most cancers that occur in the breast are breast cancers (breast carcinomas).

  • Other types of cancer, such as lymphomas (cancer of the lymph system) and sarcomas (cancer of the soft tissues), can occur in the breast.
  • Cancers from other sites can metastasize (spread) to the breast and mimic breast cancers.

These cancers are not carcinomas, or they are carcinomas that don’t start in the breast. So, they are treated differently and have different risk factors than breast cancer.

For more information on other cancers that can occur in the breast, such as lymphomas, sarcomas and malignant phyllodes tumors, visit the National Cancer Institute’s website.



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