2013-07-02

World renowned specialist Dr. Eloisa Arbustini talks about cancer prevention, its diagnosis

By Niharika Mookerjee



Dr. Eloisa Arbustini

NEW YORK: At another time and age, when medicine was still at its preliminary stage, Benjamin Franklin proclaimed, “an ounce of prevention is worth a pound of cure.” These words ring true even today as research on cancer prevention soars high while the number of people plagued with the disease is also on the rise. Breast cancer, in particular, has created a dent on the quality of life as the American Cancer Society estimates that 232,340 new cases of invasive breast cancer will be diagnosed in women in the United States in 2013 alone.

In recent months, Angelina Jolie created shock waves in the media with news of a preventive double mastectomy after being detected with BRCA 1 and 2 genes. She does not stand alone in that decision. There have been other Hollywood actresses, such as Christina Applegate, Sharon Osbourne, Giuliana Rancic, and Kathy Bates, who have sought such drastic measures.

However, cancer defies stratified definitions. The same disease may have a plurality of manifestations and stages of malignancy. But since knowledge is power, women with significant family history of cancer can make informed decisions to reduce the risk of developing cancer. Not only are they at risk, but even children, too, are at risk.

Therefore, it is imperative to realize that with early detection, cancer can, indeed, be contained. On the other hand, if it is allowed to metastasize, the prognosis may be bleak even with surgery.

In an exclusive interview to The American Bazaar, world-renowned cardiologist and gene specialist, Eloisa Arbustini, director of the Transplant Research Area of the IRCCS Foundation, Policlinico San Matteo of Pavia, Italy evaluated the myriad implications of cancer prevention and its diagnosis.

A large part of her research is dedicated to oncogenetics, in particular Hereditary Breast and Ovarian Cancer(HOBC), familial melanoma, renal cancer, Lynch syndrome, as well as other types of heritable cancers.

Arbustini graduated medical school in 1978 from the University of Bologna, Italy, and later became a specialist in Cardiology, Pathology and Genetics.  Her clinical research and activities mainly dealt with clinics, pathology and genetics of cardiovascular, respiratory, metabolic and oncologic diseases as well as organ transplantation.

She has been the main inspiration behind a center dedicated to genetic diseases in which multidisciplinary expertise join to diagnose and manage complex genetic diseases. The genetic center offers counseling, genetic testing, and post-test information to patients and families. It is also active in the context of the Breast Unit of the Hospital.

Excerpts from the interview with Dr. Arbustini:

What exactly is implied by mutations in the BRCA1 and 2 genes that are responsible for breast and ovarian cancer in women?

BRCA1 (Breast Cancer 1) and BRCA2 (Breast Cancer 2) are code multifunctional proteins that play important role in repair of DNA double-strand breaks and response to DNA damage. BRCA proteins function as tumor suppressors. Mutations in BRCA genes cause the Human Ovarian and Breast Cancer (HOBC) syndrome.

The concepts are:

• In the general population, BRCA1 and BRCA2 account for 3-5 % of breast cancer and 10-15 % of ovarian cancer.

• In high risk populations [familial HOBC, populations with founder mutations such as Ashkenazi Jewish descents, Netherlands, Iceland, and Sweden populations)] mutations in BRCA genes account for about 25% of heritable cancers; a minority of familial breast and ovarian cancers are caused by mutations in other less common known genes. Other genes, unfortunately still unknown, are likely involved in most familial cases that test negative for BRCA genes.

Is it an inherited gene mutation?

Mutations in BRCA1 and BRCA2 are heritable in an autosomal dominant fashion: carriers of mutations in BRCA genes have 50 percent probability of transmitting the mutations to offspring, both males and females.

Is it not something found in men as sometimes they too are diagnosed with breast cancer?

Men can carry mutations as women because both genes are located in autosome (non sex chromosomes). Breast cancer in man is rare and a certain percentage occurs in carriers of BRCA mutations. Daughters inheriting the mutation from the father, have the same probability of developing breast or ovarian cancer as women receiving the mutation from their mother.

What is your opinion about preventive mastectomy or hysterectomy bilateral salpingo-oophorectomy for women who have been tested positive for the BRCA 1 and 2 gene? As a precedent set by Angelina Jolie, who recently went through an extensive mastectomy, I was wondering about the pros and cons of the situation and the effect it would have on women. Is it an advisable procedure?

As a woman and doctor caring for families with HOBC, my opinion is that each woman should be correctly and extensively informed about:

• the significance of genetic tests and results,

• the predictive value of mutations in BRCA1 and BRCA2 for cancer development (based on current scientific data which could modify, either worst or better, as far as clinical and genetic series increase and the follow up further increases.

• The scientific evidences supporting preventive mastectomy or bilateral salpingo-oophorectomy in case of BRCA mutation (at present there is no alternative for primary prevention in still healthy carriers)

• the family context, which plays a major role in the emotional impact of knowing to be carrier of a mutation which predisposes to breast and ovarian cancer: women who experienced dramatic family history or assisted mothers or sisters or even daughters in their disease course are far more emotionally involved and frightened than women who are experiencing breast cancer in young age but demonstrate a negative family history.

Further, I think that each woman has the right of knowing as much as possible but also being informed correctly, in professional medical settings in which a team of multidisciplinary experts welcome their questions, doubts and concerns.

Woman who carry a BRCA mutation should be free to decide about her own choice, obviously considering that “freedom” in decisions implies not only a correct and complete information but also the full understanding of the information. In this setting time that doctors dedicate to information is the best health care investment.

About Angelina Jolie: I think that she decided on the basis of her own condition, family history, and current family commitments. Her decision must be respected but does not introduce a rule. Other women, in similar situation should feel free to decide about close surveillance or, especially very young women (for example with less that 30 years), decide to have children while maintaining a close monitoring and eventually have preventive surgery after having completed their reproductive plans, rather than taking decisions about immediate preventive surgery.

I was wondering about the pros and cons of the situation and the effect it would have on women. Is it an advisable procedure?

Preventive mastectomy as well as bilateral salpingo-oophorectomy is possible primary prevention options: each woman at risk should know about feasibility, safety, advantages, and possible complications.  They should also know that surveillance, by itself, does not prevent the occurrence of cancer.  Even the most advanced imaging studies provide diagnostic contributions mostly based on the small size of a lesion; the “malignancy and biological aggressiveness” can be evaluated on cytology or biopsy but, in that phase, the cancer is present. Very small cancers may be “aggressive” and may require chemotherapy.

The costs involved are phenomenal so the average person cannot afford such procedures, especially not reconstruction measures. What advice do you have for them?

This is a difficult question because of the health-social policies, which may vary in different countries. In Italy and other countries, the Health National System supports the reconstruction procedures. Therefore, preventive mastectomy and related reconstruction procedures as well as salpingo-oophorectomy are not charged to the woman.

I think that the possibility of a reconstruction strongly contributes to influence the decision about preventive mastectomy, especially in a young woman. However, since the decision of preventive mastectomy is also influenced by the results of genetic tests, the overall costs should include those for BRCA analysis. In my view, preventive mastectomy and reconstruction is a “right” that should be given to all women carriers of BRCA mutations, especially in multicast, early onset HOBC families.

When and where costs are charged to BRCA positive women who do not have resources to cover preventive surgery, regular appointments for clinical and imaging surveillance should not be missed. Waiting for the onset of cancer has a tremendous psychological impact and can be deleterious for socio economical and familial implications.

Can pills such as Tamoxifen seriously reduce the risks of cancer? Even without being diagnosed with cancer can one start using this medicine as preventive measure? Any other drugs you may suggest for other cancer types?

My personal view is to advise caution in information that Tamoxifen seriously reduces the risk of cancer. A recent review on the use of medications to decrease the risk for primary breast cancer reports that tamoxifen and raloxifene reduce the incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo.

Further, recent data from the Study of Tamoxifen and Raloxifene (STAR) indicate that tamoxifen reduces breast cancer incidence more than raloxifene by 5 cases in 1000 women. Both Tamoxifen and Raloxifene reduce bone fractures, but tamoxifen increases the risk of thromboembolic events, endometrial cancer and cataracts compared with either placebo or raloxifene (Ann Intern Med. 2013;158:604-14). There are countries in which Tamoxifen is entering in the management of primary prevention and others in which this is still far from clinical application. Whatever is the health policy in different countries, any decision about medications should be taken under the control of oncologists/specialists. Studies on new drugs with potential preventive effects on ovarian and tubarian cancer in BRCA mutation carriers are ongoing: indications, suggestions and decisions should be guided by specialists.

Even without being diagnosed with cancer can one start using this medicine as preventive measure?

This question is somehow answered by the prior one. A further comment should be spent about the side effects or toxicity of chronic medical treatments: if drugs are taken because of the presence of a precise disease with the aim of treating the symptoms or the cause of the disease, possible side effects can be balanced by benefits. When drugs are taken for primary prevention by a healthy individual, possible side effects may not be balanced by a proven benefit.

Any other drugs you may suggest for other cancer types?

At present there are no drugs validated for cancer prevention. Clinical trials employing novel and old molecules for new use are ongoing but at present there are no drugs for prevention of cancer.

I have in journals read that despite the surgery one could still develop cancer through breast tissue, which cannot be fully removed. How far is that true? Could there be long-term effects of such a surgery?

This depends on several factors, including the amount of residual breast tissue, the type of surgery, the mutated gene in patients with BRCA mutation. Current knowledge indicates that in the worst hypothesis, the recurrence rate is lower than 5 percent.

 Do you think apart from genetic disposition to cancer, lifestyle also plays a key role? What amendments would you suggest in maintaining good health?

Several evidences indicate that healthy lifestyle plays a role in the risk of any human disease, cancer, cardiovascular, degenerative, etc. However a single risk factor is unlikely to be deterministic for the observed multifactorial disease (and cancer remains a multifactorial disease even when the genetic predisposition is strong). Obviously, the prevention of the effects of risk factors such as wrong food, sedentary lifestyle, etc. is a general rule in human health.

In developed countries there is a tendency to aggressively deal with tumors, sometimes not even fatal, which has led to harmful effects. There is increased screening and mammograms with false positives. Exposure to CAT scans also has a damaging effect on health. What is your take on this issue?

For women carriers of BRCA mutation, the NCCN recommendations for breast cancer surveillance include monthly breast self-examination, semiannual clinical breast examination, annual mammogram, and annual breast magnetic resonance imaging (MRI). Yearly mammograms starting as early as 30-35 years of age are recommended as part of the screening strategy in BRCA mutation carriers. However, due to the role of the BRCA genes in DNA repair, BRCA mutation carriers could be more prone to radiation-induced breast cancers than BRCA negative women and, in any case, the scientific evidence is still insufficient to prove that mammogram-related exposure to radiations increases the risk of breast cancer. Although MRI is superior to mammograms and breast ultrasound in detecting early cancer and annual MRI in women between 25 and 65 years is associated with significant decrease in the incidence of advanced breast cancer compared with those not screened by MRI, mammograms identify some “ductal carcinoma in situ” with micro calcifications that are not detected by MRI.

A Reader’s Digest issue pointed out to a study in Norway that showed that not all cancerous lumps cause death. In fact, women who had cancerous lumps lived to a ripe old age without having undergone surgery or chemotherapy. How far is it accurate?

You, probably, refer to autopsy studies describing the incidental finding of Ductal Carcinoma In Situ (DCIS) and also invasive cancer in the breast of women who died of other causes. Obviously these lesions had never had phenotypical expression during life.

This information is relevant for epidemiology and for characterization of the type of lesions but does not mean that similar lesions identified in vivo, for example with imaging (mammography), are or may be non-threatening. We cannot state that the diagnosis of these lesions during life would have been harmful triggering unnecessary emotional trauma or leading to unnecessary treatments. We have no evidence that these lesions would not have become invasive life-threatening cancers if the women had lived longer. A number of reasons and mechanisms may contribute to explain these findings.

What advice do you have to people and their caregivers who are going through enormous emotional struggle with this disease?

I’m personally convinced that multidisciplinary expertise offering best health care, including primary prevention, early preclinical diagnosis and management of the disease, should concentrate in dedicated centers in which each patient/family finds competent professionals. Novel patient/family centered models of care should progressively replace old discipline centered models in which the patient is given suggestions but then is abandoned in any further step of his medical decision (searching for specialists, scheduling tests, etc.).

We have generated a center in which we are caring for a large number of families with heritable diseases, cancer. Having these families in charge means taking care of all their health problems, organize best tailored diagnostic and monitoring work-up, informing about knowledge progression and novel achievements in clinical research, support the affected members of the families in their decisions after being sure that they are fully informed about each issue matter of discussion or decision. Our role as doctors is to be at the service of patients.

Show more