Neo-adjuvant Chemotherapy For Operable Primary Breast Cancer - An Update From The Melbourne International Joint Breast Congress
Melbourne International Joint Breast Congress
I enjoyed seeing and catching up with friends. As an educational conference, it has been a good conference, and I have learnt or solidified my knowledge. And we in Wellington are doing well. Our medical oncologist and breast surgeons are up to date with their medical knowledge, and we inform and treat our patients With up to date information
As we have known for a while, there are two reasons for neo-adjuvant breast cancer treatment (where chemotherapy or endocrine therapy is given before breast surgery). One is surgical, to reduce the size of primary breast cancer to be able to perform breast-conserving surgery. The second one is oncological - to see and assess the clinical and pathological response rate in that patient to chemotherapy. Why is this oncological response important? I believe that this oncological/biological response is the most important because it gives that patient and us prognostic evidence and ability to tailor treatment (personalised medical treatment). This response is measured by looking at histology of the resected breast cancer area. There are multiple grading systems of response to neo-adjuvant therapy, but the easiest one is RCB. RCB 0 is the complete pathological response (pCR - no further cancer left), RCB 1 - minimal residual tumour left, RCB 2 - moderate residual tumour left and RCB 3 no response to treatment
Studies have found that cancer biology is important in how well they respond to chemotherapy. Her2 +ve breast cancer, as well as triple negative breast cancer (Er-ve, Pr-ve, Her2-ve), respond the best to chemotherapy. Prognosis for patients who have achieved complete pathological response (pCR) or those whose cancer has been almost completely destroyed following chemotherapy is much better than those who do not respond to chemotherapy as well.
Should we offer any more treatment for patients who have not responded as well to neo-adjuvant chemotherapy? CREATE-X trial (from Japan and South Korea) has looked at the effect of the addition of capecitabine chemotherapy in women who have not achieved good response to neo-adjuvant chemotherapy. Women were randomly selected to 2 groups: one that was given capecitabine following surgery and second group who was not given any further chemotherapy. This trial has shown that the addition of capecitabine has led to improved disease-free survival as well as overall survival in this group of patients. This trial is well designed. Its potential issues are that these results may not apply to patients outside Japan and South Korea (probably unlikely). Occasionally there is a trial that when repeated somewhere else does not confirm these results, so it would be great if there were another trial that shows these results. And like any other chemotherapy, taking capecitabine may be associated with complications. Because of all of this, we have to inform patients of this trial, and it's results and associated issues, to develop a plan of care in partnership with patients.
Patients with lobular breast cancer and patients with low-grade hormone positive cancer (ER+/PR+ or ER+/Pr- or ER-/PR+) often do not respond well to adjuvant chemotherapy and as such is likely to be avoided.
In patients who have low-grade hormone positive locally advanced breast cancer, would take endocrine therapy (tamoxifen vs aromatase inhibitor) before surgery help (neo-adjuvant endocrine therapy)?
What we know so far is that neo-adjuvant endocrine therapy does downstage (make primary breast cancer smaller in up to 75% of patients, but it does take time (3-6months). Often complete pathological response is not achieved. Achieving complete pathological response in this patient cohort does not appear to have the same prognostic benefit as in neo-adjuvant chemotherapy patients. IMPACT trial has shown that Aromatase inhibitors (AI) are associated with better breast conservation outcome then tamoxifen alone or combination (AI and tamoxifen), but there was no difference in survival.
Adding palbociclib to anastrozole (AI) also show promise, but results will be available later on this year at the San Antonio Breast Cancer Symposium later on this year. I am looking forward to hearing these results from my oncology colleagues who will attend this meeting.
Overtreatment of medical conditions has become the most talked about topic in medicine. Every medical specialty is looking at overtreatment and how to minimise it.
There are two main reasons why this is happening. First, if a patient is not going to benefit from treatment, then we as doctors are placing these patients under unnecessary risks of complications from the treatment. Secondly, we are wasting the resources that should be used for other treatments that patients would benefit from.
One part of overtreatment in breast cancer is looking at who might and who might not benefit from chemotherapy in the treatment of breast cancer. One such trial is TAILORx (Trial Assigning IndividuaLised Options for Treatment) which has shown that chemotherapy is not necessary for a majority of women with early breast cancer.
This trial included over 10,000 women who had hormone positive (oestrogen and/or progesterone positive), HER2 negative and lymph node-negative breast cancer. Their cancer tissue was tested with Oncotype DX genetic test. This test does not screen for inherited predisposition to cancer. It checks for accumulated genetic mutations profile of the woman's individual cancer.
Despite the diagnosis of early breast cancer, up to 30% of these women will develop recurrences within 10 years. Chemotherapy is recommended to reduce the risk of this relapse, but overall benefit is minimal (3-5%) of all women. All these women receive endocrine treatment consisting of Tamoxifen or Aromatise Inhibitor tablets.
Oncotype Dx test is used to predict the risk of recurrences. Women with a low score (0-10), have a low risk of recurrence (2%) and these women will not benefit from chemotherapy. Women with a high score (26 or higher), are at higher risk of recurrence and would benefit from having chemotherapy.
TAILORx has conclusively shown that women with the intermediate score (11-25) would not benefit from receiving chemotherapy.
This study allows us to make individualised treatment recommendations based on each woman's breast cancer profile.
Unfortunately, Oncotype Dx is not funded in New Zealand. It costs almost $5000.00 to have this test performed. I believe that individualised cancer treatment (based on the genetic profile of cancer) will be the standard of care in the next 5-10 years.
I hope that New Zealand will soon have this, or a similar test funded.
American Society of Clinical Oncology (ASCO) 2018. Presented June 3, 2018. Abstract LBA1
N Engl J Med. Published June 3, 2018. Abstract
The number of women having immediate or delayed breast reconstruction following mastectomy is increasing in New Zealand and Australia. Implants are commonly used for breast reconstruction, and their safety has been debated extensively since the 1960s.
Anaplastic Large-Cell Lymphoma in the Breast
Anaplastic large-cell lymphoma of the breast is extremely rare, only 1 in 3 million women without breast implants will develop it by the age of 75.
The first report of increased risk of anaplastic large cell lymphoma of the breast was published in 2008. A recent study performed by Dr de Boer and several other researchers from the Netherlands (JAMA Oncol in 2018) has confirmed this.
Dr de Boer et al. have looked at all women in the Netherlands who have developed anaplastic large-cell lymphoma of the breast and compared these patients to those with other types of breast lymphomas.
Presence of implants was only associated with an increased risk of anaplastic large-cell lymphoma, not other types of lymphomas. This risk is 421 times higher for women with implants in comparison to those without implants. But the absolute risk is still low. By the age of 75, only one of 6920 women with implants will develop this type of lymphoma.
Dr de Boer and her colleagues have also looked at specific types of implants that may be associated with increased risk. They have found out that macrotextured implants are associated with a more significant risk.
The cause why implants may lead to an increased risk of anaplastic large-cell lymphoma is not known. It is postulated that it may be due to an immune system response or an inflammatory reaction to implants.
It is not known whether the increased duration of presence of implants is associated with increased risk.
Having breast implants does increase the risk of developing a breast anaplastic large cell lymphoma. This risk is still small, only 1 in 7000 women with implants will develop it.
If you are considering having implant-based reconstruction, please discuss with your plastic or breast surgeon type of implants used and their risk of developing this type of lymphoma, as well as any other complications.
I am Breast, Endocrine and General Surgeon.
Wakefield Specialist Medical Centre
99 Rintoul St, Newtown
Waikanae Specialist Centre
Boulcott Specialist Centre
666 High Street, Boulcott