Breast pain

HRT and Breast Cancer: What you need to know – By Prof Zoe Winters & Miss Jeannie Yoon

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The mere mention of HRT can spark fears of breast cancer, but should it? Breast surgeon Professor Zoe Winters and Consultant Gynaecologist Jeannie Yoon set the record straight.

Navigating the Menopause can be a huge challenge for many women. It can be a strange and isolating time for some as despite being well informed, there remains a taboo about acknowledging it and discussing it openly. 

Approximately 95% of women will go through the Menopause between the ages of 45 and 55 years with an average age of 51 years. The symptoms can range from minor to debilitating and include hot flushes, night sweats, joint and muscle pain, ‘brain fog’ often described as ‘word salad’, poor concentration, disturbed sleep, low mood, anxiety, vaginal dryness, a reduction in libido and bone fractures in later life. These Menopausal symptoms typically continue for 5 years after the last period and for around 10% of these women, they can last up to 12 years. 

It is important to remember that each woman will experience this journey differently. For many this natural transition can be relatively seamless, but for 25%, their personal and professional lives can be significantly affected. 

In the past, clinicians approached women with menopausal symptoms with a rather fixed approach of ‘one size fits all’, but we now know that an integrated approach based on the individual woman’s needs works best. 

A healthy lifestyle can minimise the effects of the menopause and certain complementary and alternative therapies may help. The most widely used and effective treatment for menopausal symptoms is Hormone Replacement Therapy (HRT) but only around 1 million women in the UK are currently using this.  

“…there is now a generation of women who have been denied the opportunity of an improved quality of life during their menopausal years…” 

HRT was first available in the 1940s before becoming widely used in the 1960s when it revolutionised the management of the menopausal woman. However, in 2002 and 2003 the results of the USA Women’s Health Initiative (WHI) and the UK Million Women Study (MWS) were published and their findings raised concerns about the safety of HRT, including the risk of Breast Cancer.  There was widespread publicity which resulted in panic amongst clinicians and users. The number of women taking HRT fell by around 60%, and that has not changed significantly in the intervening years. 

As a result there is now a generation of women who have been denied the opportunity of an improved quality of life during their menopausal years. 

breast mammogram harley street emporium

It is important to note that the WHI study had flaws. It demonstrated adverse effects of HRT in the older postmenopausal women (over the age of 60 years) but this is not the age group of women that presents with the new onset of menopausal symptoms that occur mainly in the late 40s to 50s. 

“…other factors like lifestyle issues, obesity, alcohol consumption and smoking can have a greater effect on Breast Cancer risk than HRT…”

When advising women in the 40-50 age group, their age specific risk needs to be taken into consideration and the data suggests that the overall risk benefit profile is more favourable for women ages 50 to 59 years. Of course a full medical history is vital when assessing suitability for HRT as other factors like lifestyle issues, obesity, alcohol consumption and smoking can have a greater effect on Breast Cancer risk than HRT. According to NICE, obese women have a 6 times higher risk of developing Breast Cancer than the extra risk associated with combined HRT. 

The current consensus is that HRT taken for less than 5 years does not significantly increase the risk of Breast Cancer, but studies have shown that after 5 years of use, a small increase in risk is possible. Once HRT has been stopped, this risk appears to return back to baseline, suggesting that HRT may promote the growth of Breast Cancer cells that are already present if HRT is taken for more than 5 years after the age of 50 years. In some women, however, there is no evidence that HRT causes Breast Cancer.  

In 2019 the highly reputable journal, The Lancet, published a large meta-analysis looking at women with a normal body mass index who started HRT in their 40’s-50’s. It confirmed that different types of HRT are associated with different risk for women who started HRT in their 40’s-50’s.   

womens health concern breast cancer risk

Oestrogen-only HRT does not appear to increase the risk of breast cancer (1 in 200 women), while there appears to be a small increased risk with long-term (>5 years) use of combined HRT (oestrogen and progesterone) preparations (1 in 50 women), compared to the general population of women at 50-69 years of age who have never taken HRT ( 1 in 16). Consequently, breast surgeons recommend more frequent (annual versus 2 yearly) mammograms plus ultrasound in individual cases based on perceived increased risks of breast cancer.  

The type of HRT and the ways it’s taken or used can influence risks too and should be discussed in detail with your expert clinician. For example, the safest form of HRT is oestrogen only versus combination oestrogen and progesterone recommended in women with an intact uterus. Transdermal or topical oestrogen is safer than oral administration, as the former bypasses being metabolised through the liver, thus avoiding the less safer liver metabolites of oestrogen. The type of progesterone is also thought to play a role. 

“…Women now live longer in the post-menopausal period than in their reproductive phase and it is therefore of paramount importance that we focus not just on extending their lives, but to ensure that they have a quality of life that they duly deserve…”

Another important factor to note is the fact that if HRT is commenced at an earlier age due to Premature Ovarian Failure, the use of HRT up to the age of 50 years does not increase the breast cancer risk any more than in women who continue to have periods up to the age of 50 years. The additional risk from HRT only applies if it is then taken for more than 5 years after the age of 50 years. 

This does not, however, mean that you have to stop taking HRT after the age of 50.

Women are often told that after 5 years or after the age of 60 that they should stop too, but this is not the case. If you are aware of the risks and benefits and your health is closely monitored you can opt to continue.

mammogram-harley-street-emporium

There are numerous health benefits derived from HRT in women who are symptomatic with the earlier timely recommended use of HRT being the most beneficial. Exposure to long term, or longer than 5 years of uninterrupted oestrogen and progesterone is just one of a number of breast cancer risk factors that may also increase breast density. Other breast cancer risk factors comprise family history, gene mutations and atypia (slightly abnormal appearing cells) on tissue biopsies, and finally common gene variants involving population or background genes called single nucleotide polymorphisms or SNPs.  

Currently, there are exciting possibilities to offer all women over 40 years of age access to testing of their individual Breast Cancer Risk Score whereby if they are high risk, we would recommend annual clinical examination and breast mammogram screening.  In women with prohibitively dense breasts, we can include focused ultrasound and breast MRI. There are two large high-quality studies in the USA and Europe evaluating the benefits of women selecting mammography based on personalised risk. We can now offer this testing in private care. 

As a Clinician in modern times, we are aware that women now live longer in the post-menopausal period than in their reproductive phase and it is therefore of paramount importance that we focus not just on extending their lives, but to ensure that they have a quality of life that they duly deserve. It is therefore essential that we work together in an integrated fashion to empower women with accurate and appropriate information for them to make the right choices for themselves and to treat them as individuals. 

You can find out more about the authors of this article here:

Miss Jeannie Yoon – Consultant Gynaecologist and Obstetrician  

Professor Zoe Winters – Consultant Breast Surgeon and Breast Specialist  

London Breast Health

Harley Street Emporium

Close up of Genes

Genetic testing and what it means – By Prof Zoe Winters

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Personalised genetic testing in breast cancer patients and what it means.

Hereditary breast cancer – inherited germline mutations 

This means the abnormally functioning genes we inherit that predict a high lifetime risk for developing breast cancer ranging from 35-80% by 80 years of age. Inherited breast cancer is rare and causes only 5% of all breast cancers. Currently the guidelines for testing high risk genes has expanded with lowered thresholds for genetic testing of the following genes: BRCA1, BRCA2, PALB2, CHD1, P53 and PTEN. We test different numbers of genes based on family history of breast and ovarian cancer or other cancers that indicate the need for syndromic testing. These other cancers include: prostate; pancreatic; colonic; stomach; thyroid; and uterine cancer amongst others. We use established algorithms on which to base referring you to a specialist geneticist. 

In the last 5 years, we have tested women presenting with early breast cancer who are: <45 years of age; have a triple negative (negative for oestrogen, progesterone and HER2) breast cancer <70 years of age; and bilateral breast cancer <60 of age. 

Hereditary gene testing focuses treatment recommendations on: risk-reducing breast and ovarian surgery, including high-risk breast screening and biological risk-reducing chemoprevention using drugs like Tamoxifen or Aromatase Inhibitors (AIs) for 5 years. Importantly, we should also check for hereditary genes in advanced breast cancer where the cancer has returned or spread to other body sites. 

Mutations or abnormal function of the BRCA1/2 genes means that cancer cells cannot detect damages to their genetic material or DNA, and also cannot repair their damaged DNA. This is why cancers occur at such high rates in these patients. This genetic deficiency can be used as a treatment advantage when combined with drugs that block sensors of DNA damage and repair. These drugs are called PARP inhibitors and they effectively kill BRCA1/2 abnormal cancer cells where the BRCA genes aren’t functioning. The PARP inhibitors sensitise BRCA cancers to the DNA damaging effects of chemotherapy and radiotherapy. 

The platinum types of chemotherapy like Carboplatin are also particularly effective in killing BRCA mutated breast cancers. 

These drugs are also highly effective in treating triple negative breast cancers (no expression of oestrogen, progesterone or the HER2 gene) that carry mutations of the BRCA 1 (70%) or BRCA2 (20%) genes. 

The abnormal DNA repair pathways conferred by these gene mutations can be used for treatment advantages. 

The more recent testing of the PALB2 gene (Partner and Localiser of Breast Cancer 2 (BRCA2)) functions together with the BRCA2 gene and serves as an additional drug-able target for cancer treatments. All women previously undergoing BRCA testing before 2014 should be referred for retesting of BRCA1/2 and PALB2.

Women with advanced breast cancer that carried BRCA mutations were treated with PARP inhibitors in two breast cancer trials called OLYMPIAD and EMBRACA. They both showed a significant improvement in cancer-free survival. 

Currently, there are many breast cancer trials evaluating PARP inhibitors either at the pre-surgery (neoadjuvant) or post-surgery (adjuvant) stages of treatments in women with BRCA abnormal genes. 

Genomic gene expression signatures in early oestrogen (ER+) positive breast cancer to guide chemotherapy 

A number of commercial assays are used to quantitate levels of 10 -100 different gene expressions using messenger RNA in what is known as a “transcriptome”. This is not the same as a germline mutation that occurs in hereditary breast cancers or advanced breast cancers (described above). Until now, we have relied on cancer histological grade and proliferation index (ki67), but the transcriptome profile provides us with much more prognostic/predictive information on the full spectrum of breast cancers over and above routine breast cancer staging.

The transcriptome predicts 10-year overall survival in women with early stage oestrogen positive (ER+) lymph node negative disease evaluated in the TAILORX trial. The 21-Gene OncotypeDx recurrence score identifies those women who will benefit from chemotherapy after surgery, and allows us to recommend personalised treatments. 

Another trial called MINDACT has also shown that the 70 gene MammaPrint assay determines when chemotherapy is beneficial for increasing survival in addition to ER+ endocrine treatment. Young age <50 years is a key factor when interpreting the gene recurrence scores, with greater benefits of chemotherapy in younger women compared to those >50 years. This may be due to a chemotherapy-induced menopause. OncotypeDx can also be used to predict recurrence scores in lymph node positive patients, who may avoid chemotherapy without compromising cancer outcomes. 

Other genomic assays such as the 12-gene EndoPredict and the PAM-50 have not been as fully evaluated in studies comparing chemotherapy versus no chemotherapy. It is possible that gene assays may also predict when to extend or prolong endocrine treatments such as Tamoxifen or aromatase inhibitors from 5 to 10 years, however there are no high-quality studies validating this at present.  

Genomic sequencing in advanced breast cancer to increase drug treatments 

Testing acquired or somatic mutations of 200-600 genes is based on the relatively frequent mutations that occur between the primary breast cancer and the subsequent recurrence or relapse of breast cancer. Testing can be done by sequencing genes in the cancer tissue or the circulating free cancer DNA (ctDNA), where cancer cells release their DNA into the circulation when they die. The gene testing of ctDNA correlates well with that of the cancer tissues and should be evaluated first. Levels of ctDNA can be used to predict worse cancers that are progressing, and are not responding to treatments after only two weeks. 

Acquired mutations as cancers evolve or that occur after treatments have been shown in ER+ cancers to involve the oestrogen resistance gene (ESR 1) that confers resistance to aromatase inhibitors, which means these drugs cease to be effective. The commonest mutations in 40% of ER+ cancers also affect the PI3 kinase pathway that can be targeted by specific drugs. 

Germline testing of BRCA1/2 selects patients who will benefit from PARP inhibitors and carboplatin chemotherapy. Triple negative cancers may also harbour mutations in the PIK3 kinase pathway that can be used as drug-able targets.

Molecular testing of breast cancer is a rapidly evolving field and is here to stay! 

References:

Litton JK, Burstein HJ, Turner NC. Molecular Testing in Breast Cancer. Am Soc Clin Oncol Educ Book. 2019 Jan; 39: e1-e7. doi: 10.1200/EDBK_237715.

More information:

Family history and breast cancer – Breast Cancer Now

NVH news and articles/breast health and genetic testing

Breast pain

A guide to Breast Pain – By Professor Zoe Winters

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A breast surgeon’s guide to Breast Pain (BP) – the second commonest One-Stop breast problem

 

I see many women in the UK with breast pain (BP) and over the years, my medical understanding of how to explain its rationale and treatment has evolved. My key aims in a One-Stop breast clinic are to communicate clearly and reassure based on the current medical evidence.

Breast pain (BP) is like the “common cold”. It affects 70-80% of women in the One-Stop breast clinic, but rarely are we able to attribute it to a specific cause. That’s because it is multifactorial. We do not know about genes predisposing to benign conditions, but there are likely to be other female members of one’s family who have suffered from this syndrome.

BP is not a risk factor for breast cancer and is very rarely associated, occurring in about 

0.4 – 0.8% of cases. Breast density (increased amounts of breast tissue) is a risk factor for breast cancer, and may be linked to persistent BP extending over 3 to 8 years. Larger breast volume is also a contributing factor with “increased strain” on connective tissue ligaments.

The onset of BP can be sudden in women in their 30’s or 40’s with only 15% occurring in post-menopausal women. 

 

Overall Breast Pain is a benign condition without an obvious single cause, however it still requires assessment by a healthcare professional. 

 

Cyclical BP – 70% of women (onset in 30’s) 

This is described as “coming and going” (cyclical) and an indicator for recurring BP later in life until one reaches menopause. It tends to be widespread in the breast occurring in more than one location. We attribute this type of BP to the increased hormonal sensitivity of normal breast tissue of unknown causes. Blood hormone levels are normal and there is no evidence of breast disease. 

Possible contributing factors are:

  • Medications: Antidepressants such as Selective Serotonin Uptake Inhibitors 

Up to 20% of BP will resolve within 3 months, and 60% of BP will recur within 3 years.

Older onset BP – 25% of women (onset in 40’s)

This is more constant and is localised to a “trigger spot” or a single area particularly in the central nipple region and in the lower inner breast. 

This type of BP is more likely to be “inflammatory” which isn’t due to a  bacterial infection, but rather to a “chemical phenomenon” that occurs in the ageing breast ducts where the walls of the hollow breast ducts (milk ducts) become thin causing duct dilatation called “duct ectasia”. A chemical inflammation occurs due to stagnant breast duct secretions and can cause local BP. 

Constant BP usually isn’t hormonal, and 50% resolves spontaneously. 

Why should BP occur in only one breast?

Embryology (development of the human embryo) explains this because it provides a logical explanation. We develop in two potentially symmetrical halves from the spine behind, extending to the front of our bodies to join in the midline. Therefore, none of us are totally symmetrical! This applies to face, hands, feet or breasts!

Each milk duct line is developmentally separate extending from the armpit to the groin on the right and on the left, respectively. So our breasts aren’t  symmetrical in shape, size or in the amounts of breast tissue they contain and in biochemical responses to particular triggers.

The breast tissue within each breast is not equivalent. Most breast tissue is located in the upper outer breast, central breast and where the breast attaches to the chest wall, called the infra-mammary fold. This means that each breast has its own potential to develop cyclical or constant BP. 

In fact, most BP is one-sided in 76% and affects both breasts in 24% of patients. 

Treatments 

A comprehensive overview of all randomised trials looking at treatments for BP have provided clear evidence for the following recommendations:

First line treatment for BP:  Topical Voltarol gel which is a non-steroidal anti-inflammatory where there is far greater benefit compared to unwanted side-effects. There is one randomised clinical trial. The magnitude of the benefit on BP from a number of studies showed a 70-92% reduction in pain. 

Second line treatment: Selective Oestrogen Receptor Modulators (SERMS). 

Raloxifene was shown in trials to prevent breast cancer and to treat osteoporosis. It acts by selectively blocking the oestrogen receptor The recommended dose for treating BP is recommended at half the dose routinely used in preventing osteoporosis (30 mg orally daily) for 6 months. It can reduce BP up to 92%.

The other SERM option is Tamoxifen, the drug we use to treat breast cancer patients, that can be used at half the dose (10 mg orally daily) for 6 months. Tamoxifen is however less effective than Raloxifene in reducing BP (45% versus 92%) and has more side-effects.

Neither Raloxifene nor Tamoxifen are registered for BP treatment despite having been shown to be effective in randomised clinical trials. Raloxifene is a preferred second-line choice for severe BP as it is associated with fewer side effects than Tamoxifen. 

Both above treatments should only be used under the supervision of your surgeon and ONLY in those women where Voltarol gel is ineffective, or their BP is severe and is affecting a woman’s quality of life. 

You should still get your breast pain assessed by your doctor or another health professional.

Book an appointment here 

References

Goyal A BMJ Clin. Evid. 2011 Jan 17; 2011: 0812.

https://pubmed.ncbi.nlm.nih.gov/21477394/

Jokich P J Am Coll Radiol. 2017 May; 14(5S): S25-S33.

https://pubmed.ncbi.nlm.nih.gov/28473081/

Hafiz SP, Barnes NLP, Kirwan CC. Clinical management of idiopathic mastalgia: a systematic review. J Prim Health Care. 2018 Dec;10(4):312-323.

https://pubmed.ncbi.nlm.nih.gov/31039960/

A diagram of the one-stop process

The benefits of a One-Stop Breast Clinic By Professor Zoe Winters

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According to the current UK guidelines for breast cancer screening, mammography is recommended for all women between 50 and 71 years old, every 3 years. Some areas increase the age range to 47 to 73 years old. Breast cancer risk increases with age, however, it can be useful to speak to a breast specialist at a younger age. Professor Zoe Winters, Consultant Breast Surgeon, talks about the importance of early diagnosis and the benefits of a One-Stop Breast Clinic.

The importance of breast cancer prevention

Breast cancer prevention is a goal that all doctors and nurse practitioners in the field aspire towards. It starts with clear communication on personal breast awareness and breast self-examination and is also based on how soon and how often women should have mammograms and /or ultrasound (US).

We now have the benefits of digitally enhanced mammograms, including 3-D tomosynthesis. Doppler-assisted breast ultrasound (US) that measures increased blood flow in a specific lump or area of the breast may also increase interpretative accuracy. US is
used to guide needle tissue biopsies, to accurately confirm the correct diagnosis of any breast lump.

When is it a good time to have mammograms?

There is no consensus worldwide on how soon and how often women should have mammograms.

The benefits of mammogram screening in women in their forties have recently been reported by the UK Age trial. The study randomly invited women from 39/40 to 48 years of age to have yearly screening mammograms (group of 53,000). This test group was compared to a standard care group undergoing mammograms from 50 years of age and repeated every 3 years (group of 162,000).

At 10 years, there were less breast cancer deaths in the early screening mammogram test group (83), compared to 219 in the standard of care 50-year-old plus group. This amounted to a significant or 25% reduction in breast cancer deaths.

Other European countries and the USA have practised screening mammograms from either 40 or 45-years of age every year.

Why UK guidelines recommend breast cancer screening for women over 50 only?

In the UK, the National Screening Committee and the NHSBSP Publication No 49 set the national Breast Cancer screening guidelines.

Breast cancer incidence peaks between 50 and 70 years of age. The wider the age range, the greater the chances to incur an over diagnosis, where women are more likely to be diagnosed with benign, harmless forms of cancer.

High-intensity international screening programs showed that after 25 years of follow-up, >50% of mammogram-detected small cancers were over-diagnosed. This means an early diagnosis of a cancer that would not otherwise have shortened that woman’s survival.

However, could these improved breast cancer death rates be the results of much improved current breast cancer medical/drug treatments rather than early mammogram screening?

Over diagnosis can have a negative impact on women’s mental wellbeing and potentially discourage them from participating in further screenings in the future.
Although it is important to know that breast imaging examination can’t distinguish between harmful and benign types of cancer, this is the only and most efficient tool for early diagnosis.

Knowing your breasts is the first step towards early diagnosis

The Breast Cancer Now online publications website is an excellent source of patient information that clarifies key changes that every woman should be aware of and alerted to when examining their breasts.

Breast cancer symptoms you should pay attention to

Women should be aware of any changes to either of their breasts, however small it may seem. This may be a change in the shape or size of the breast and/or the nipple. Any concern about a persistent lump is important.

Many of these concerns do not automatically mean that there is breast disease, but the latter can only be ruled out through a specialist examination and breast imaging such as mammograms and/or ultrasound.

Other concerns that should be investigated are:

  • breast pain
  • nipple discharge
  • nipple rashes
  • permanent nipple indentation
  • breast skin dimpling

Not all the changes are a sign of cancer

The breasts develop from two separate milk duct lines, and therefore a “normal asymmetry” is possible in terms of their shape, size and amounts of breast tissue.

Most breast lumps are not disease, but relate to normal breast tissue that is asymmetrical with unequal distributions of breast tissue that is not “a smooth surface under the skin”.
The latter results in the sense of a lump, whereby you may be feeling normal tissue.

Neither cysts, nor breast pain are risk factors for breast cancer in over 95% of cases but should still be investigated at a One -Stop Breast Clinic.

How does the One-Stop A diagram of the one-stop process Breast Clinic work?

Most normal lumps are fluid-filled cavities called cysts that occur based on normal ageing of the breast milk ducts or tubules draining the breast milk sacs or terminal lobules.
Any solid breast lump usually requires a tissue biopsy to determine its diagnosis.

Women of any age who are concerned about their breasts can contact our One-Stop rapid diagnosis Breast Clinic.
This is how the One-Stop Breast Clinic works:

  • Step 1 – Specialist Consultation

If you are concerned about any changes in your breasts or have risk factors, you can book an Outpatient appointment with a Breast Surgeon at New Victoria Hospital. The specialist will listen to your concerns, ask questions about your lifestyle, family history, and assess your case.

  • Step 2 – Appropriate examination

After a clinical breast exam, if there is any suspicion of tissue abnormalities, these cases are acted upon immediately. Your Consultant Breast Surgeon will book the appropriate Imaging exams to further investigate your case.

  • Step 3 – Tissue biopsy

On the same day of your Imaging examination, you can be offered a tissue biopsy. This is a non-invasive procedure to collect a sample of your breast tissue with a needle, for a precise diagnosis.

  • Step 4 – Results

Results from a tissue biopsy may take up to 72 hours as they are discussed within a dedicated multi-disciplinary team meeting, comprising radiologists, pathologists, surgeons, and oncologists. You will be reassured and guided
through the treatment options.

The benefits of the One-Stop Breast Clinic

Many women find One-Stop Breast Clinics very beneficial.

A new randomised trial in the USA called the WISDOM study that stands for “Women Informed to Screen Depending on Measures of Risk” is a study that is often shared with many women in One-Stop Breast Clinics.

This trial uses a personalised breast cancer risk score in the past 5 years. This score is based on age, race, affected first degree relatives, prior breast biopsies, proliferative breast conditions with atypia (abnormal cells), breast density score assessed using a BI-RADS and genomics (high/moderate penetrance genes) and 96 polygenic risk score (lower risk common genetic variants).

The rapid diagnosis One-Stop Breast Clinic aims to provide results at the same time as the consult in over 95% of patients.

The One-Stop Breast Clinic:

  • facilitates a referral to a specialist consultant clinical geneticist
  • provides you detailed information sheets on “Genes and Families” (Breast Cancer Now publications, ref 4) that gives you a clearer idea on gene risk factors
  • gives you peace of mind sooner with a fast diagnosis process

When you should have your breast checked by a specialist

Although the current UK guidelines suggest mammography screening for women over 50, there are many cases where a breast examination either through a Consultation, an ultrasound scan or mammography can give you peace of mind.

You should consider visiting the One-Stop Breast Clinic if:

  • You have a family history of breast cancer and/or ovarian cancer
  • You are concerned about a change in the skin or tissue texture of your breasts
  • You have done a genetic test before 2014, as more in-depth, specific gene testing is available
  • You want to avoid long waiting times for your results

The benefits of the One-Stop clinic – News at New Victoria Hospital

Patients experience of the One-Stop Breast Clinic

One-Stop Breast Clinic Locations