October is Breast Cancer Awareness Month so we’re putting the spotlight on some of the best recent research on breast cancer treatments. If you’re making a decision about treatment, it’s really important that you and your doctor have up-to-date, reliable information to help you. This is what Cochrane reviews are for. They are independent, systematic reviews, pulling together health research on prevention, treatments and diagnostic tests, for particular patient groups and settings, establishing whether there is conclusive evidence and what it tells us. Sometimes the evidence isn’t very good, or missing altogether; it’s important to know when there are uncertainties about treatment. They are updated regularly, ensuring that treatment decisions can be based on the most up-to-date and reliable evidence.
Trastuzumab – balancing benefits and risks
First, good news about trastuzumab (Herceptin®), a drug that blocks the activity of HER2, a protein that makes cancer cells divide and spread much more quickly than other cancer cells or normal cells. About 15% to 20% of breast cancers are HER2-positive and the outlook for these women has been poorer than those with HER2-negative disease.
A new Cochrane review has pooled evidence from clinical trials on women with advanced breast cancer and found that trastuzumab reduces cancer progression by more than a third. This benefit must be considered alongside the small but increased risk of developing heart problems, though most of these are reversible. Women taking trastuzumab survived for longer overall too and this effect was probably even better than the results suggest, as the authors of this editorial explain:
“when an effective treatment is being tested, patients who start to develop resistance to that treatment are usually (and completely appropriately) then given further treatment. This is good for the patient (she lives longer) but bad for science (the true effect of the tested treatment is diluted). So we welcome the apparent beneficial effect of trastuzumab on survival, but we suspect that it is better than quoted.”
The women in these trials were given trastuzumab for the first time. We don’t know how effective it is for women who relapse after being treated with it.
The same team also did a review of trial evidence for trastuzumab used to treat early breast cancer and found that for these women too, trastuzumab improves both overall survival and disease-free survival. As for women with advanced breast cancer, the risk of death is reduced but the risk of heart toxicity increased. They conclude that “in women at higher risk of recurrence and with no signs of a weak heart, trastuzumab offers far more benefits than risks. The balance of risks to benefits in patients at lower risk of recurrence (e.g. a small rather than a large tumour) must be carefully evaluated.”
Choices for older women
Women under 70 with early-stage, oestrogen-sensitive breast cancer, are almost always offered surgery plus endocrine therapy, drugs that stop cancer cell growth by blocking their oestrogen receptors. Older women are often treated just with these drugs and this is known as primary endocrine therapy. Tamoxifen has been used in this way since the 1980s, on the basis that older women are more likely to have oestrogen-sensitive breast cancer and may also be less fit for surgery.
A Cochrane review has pulled together evidence on how surgery, with or without endocrine therapy, compares to primary endocrine therapy for these women. They found that the choice of treatment made no difference to survival but women who had surgery were less likely to relapse. Both treatments had side effects. Problems after surgery included tingling or numbness on the arm on the side of the surgery, and psychosocial problems, while side effects of tamoxifen were hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion.
This evidence puts surgery ahead of primary endocrine therapy in terms of local disease control and fewer ill effects but primary endocrine therapy is an option for women who don’t want surgery or are not fit enough for it.
Surgery for advanced breast cancer?
In the past women with advanced breast cancer were not offered surgery, but now it’s thought that it could improve survival. A Cochrane review looking at whether surgery is a useful treatment for women with metastatic breast cancer is under way. The review team is aware of several current trials comparing surgery plus chemotherapy with chemotherapy only for women who had metastatic breast cancer when first diagnosed, which should be publishing their first results soon.
Update: this review was published in March 2018. The review includes just two studies with 624 women. Neither study reported on quality of life or breast cancer-specific survival. Very low quality evidence means that there is continued uncertainty about the impact of surgery on overall survival. It may improve local progression-free survival and probably worsened distant progression-free survival. There are still ongoing trials that may change the findings in a future update of the review.
Considering your options
Knowing what the evidence says is important for decisions about treatment and your health practitioner will bring to this their professional expertise too. As well as these, your values and preferences are vitally important. The reviews we’ve looked at here show that, like many treatments, there are things to weigh up and you will need to decide what’s most important to you.
Decision aids can help
There are resources that are specially designed to help people make decisions about difficult healthcare options. They are based on reliable evidence and they can help you think through what might be best for you. You can find patient decision aids for a number of health conditions (though not breast cancer) on this NHS Shared Decision Making website. One type of decision aid is an options grid and you can see one for breast cancer surgery here on the patient.co.uk website We also have evidence from a Cochrane review showing how decision aids can be helpful to people making treatment choices and you can read my blog about that here.
See what your doctor sees
NHS doctors use an internet resource called the Map of Medicine to help them work out the best treatment options and you can access this free resource too, so you see what your doctor sees. It’s available from NHS Choices here. The NHS Choices website has lots of other useful information about breast cancer too.
Hearing from other patients can help too
You might also like to visit healthtalk.org Dr Anne McPherson set it up, with another doctor-patient Andrew Herxheimer, when she was diagnosed with breast cancer and couldn’t find anyone to talk to about what it was really like to have the disease. It’s a fantastic resource from patients, for patients, offering a wealth of reliable health (and other) information, shared experiences and support. You can also hear from women about the realities of living with breast cancer on Breast Cancer Care’s #hiddeneffects campaign page here, as well as reading their blog and following them on twitter @BCCare #hiddeneffects
You can follow us on Twitter @CochraneUK @SarahChapman30. You might also like to check out the many Cochrane summaries on breast cancer topics – these are summaries of Cochrane reviews written in plain English, with links to the full reviews and sometimes to other resources. Just go to the Cochrane Summaries site and type breast cancer into the search box.
Page last updated: 30 May 2018
Balduzzi S, Mantarro S, Guarneri V, Tagliabue L, Pistotti V, Moja L, D’Amico R. Trastuzumab-containing regimens for metastatic breast cancer. Cochrane Database of Systematic Reviews 2014, Issue 6. Art. No.: CD006242. DOI: 10.1002/14651858.CD006242.pub2.
Cochrane summary and podcast http://summaries.cochrane.org/CD006242/BREASTCA_efficacy-and-safety-of-trastuzumab-in-metastatic-breast-cancer
Moja L, Tagliabue L, Balduzzi S, Parmelli E, Pistotti V, Guarneri V, D’Amico R. Trastuzumab containing regimens for early breast cancer. Cochrane Database of Systematic Reviews 2012, Issue 4. Art. No.: CD006243. DOI: 10.1002/14651858.CD006243.pub2.
Cochrane summary and podcast http://summaries.cochrane.org/CD006243/BREASTCA_efficacy-and-safety-of-trastuzumab-in-early-breast-cancer
Morgan J, Wyld L, Collins KA, Reed MW. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD004272. DOI: 10.1002/14651858.CD004272.pub3.
Breast surgery for metastatic breast cancer. Cochrane Database of Systematic Reviews 2018, Issue 3. Art. No.: CD011276. DOI: 10.1002/14651858.CD011276.pub2., , , , .
Stacey D, Légaré F, Col NF, Bennett CL, Barry MJ, Eden KB, Holmes-Rovner M, Llewellyn-Thomas H, Lyddiatt A, Thomson R, Trevena L, Wu JHC. Decision aids for people facing health treatment or screening decisions. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD001431. DOI: 10.1002/14651858.CD001431.pub4.