Gynaecomastia and breast cancer in men
BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39511.493391.BE (Published 27 March 2008) Cite this as: BMJ 2008;336:709All rapid responses
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In their review “Gynaecomastia and breast cancer in men” Niewoehner
and Schorer [1] mention that physiological gynaecomastia is frequent in
older men, and that physiological gynaecomastia requires no treatment
unless accompanied by pain or significant embarrassment. This statement
may, however, mislead some to think that gynaecomastia in older men should
not be examined. Here, we present a case and argue that gynaecomastia
ought to be evaluated by specialists.
A 64-year-old male was referred to our clinic because of bilateral
gynaecomastia with a slight tenderness on the left side (Figure 1). He was
referred after 3 visits at his general practitioner and was seen in our
department 5 months after his first symptom. When palpated he had a
typical gynaecomastia on the right side. On the tender left side he also
had some glandular tissue that could resemble gynaecomastia, but in
addition eccentric, irregular and hard tissue resembling breast cancer
located in the upper left quadrant. This was, however, displaceable from
the underlying fascia. A palpable enlarged lymph node in the left axilla
supported the suspicion of malignancy. A core biopsy and later mastectomy
revealed an oestrogen and progesterone receptor positive invasive ductal
carcinoma with local spread to the sentinel axillary lymph node. In
addition to the breast enlargement the patient history was unremarkable
except for a noticeable daily alcohol intake.
Can this patient’s history and clinical presentation have caused a
delay in getting the right diagnosis? Whether the general practitioner,
who saw the patient 3 times before he was referred, was mislead by the
information of the patients daily alcohol intake or the knowledge that
physiological gynaecomastia in older men is quite prevalent cannot be
clarified, but apparently the general practitioner did not suspect the
patient to have breast cancer.
In our clinic, we annually get approximately 200 men referred due to
breast enlargement, and it is our experience that many general
practitioners find it difficult to evaluate the male breast disorders.
Often breast cancer is suspected in obvious benign cases, or as we
described here overlook an obvious malignant case. It is not easy for an
inexperienced to evaluate enlarged breasts, because the clinical
presentation is versatile [2]. Niewoehner and Schorer among others [3,4]
indicated that symptoms and signs are often unspecific, when it comes to
discriminate between benign and malignant cases. The presence of
gynaecomastia does not exclude breast cancer, as up to 40% of men with
breast cancer have gynaecomastia. Also, tenderness and pain are unspecific
symptoms, as they also often are associated with gynaecomastia.
Male breast cancer is rare, but besides a general increase in
incidence, it is also increasing with increasing age. In our opinion this
emphasise that also older men with breast enlargement ought to undergo a
physical examination by experienced physicians, especially when symptom
progression takes place over a shorter period.
Reference List
1. Niewoehner, C. B. and A. E. Schorer. "Gynaecomastia and breast
cancer in men." BMJ 336.7646 (2008): 709-13
2. Braunstein, G. D. "Clinical practice. Gynecomastia." N.Engl.J Med.
357.12 (2007): 1229-37.
3. Lanitis, S., et al. "Diagnosis and management of male breast
cancer." World J Surg. 32.11 (2008): 2471-76.
4. Mathew, J., et al. "Primary breast cancer in men: clinical,
imaging, and pathologic find-ings in 57 patients." AJR Am J Roentgenol.
191.6 (2008): 1631-39.
Competing interests:
None declared
Editorial note
The patient whose case is described has given his signed informed consent to publication.
Competing interests: No competing interests
sir
niewoehner and schorers review on gynaecomastia and breast cancer in
men,and subsequent comment by john colin, reminded me that i had long
intended to provide an easy to read guide for drugs reported to have
gynaecomastia as a possible side effect for use in our breast clinic.
this has now been completed by a search of the bnf and pubmed web-
sites
anyone wishing to obtain an alphabetical list to speed up clinic
checks will find it on
http//www.breastclinic.co.uk/drugsthatcausegynaecomastia.php
Competing interests:
None declared
Competing interests: No competing interests
In their review of gynaecomastia and breast cancer in men,1
Niewoehner and Schorer omitted the clinical classification of
gynaecomastia. The system developed by Simon et al2 is the most commonly
used classification and helps to understand the surgical correction of
gynaecomastia. This classification is based on the extent of breast
enlargement and the presence or absence of excess skin:
• Grade 1: minor breast enlargement with no excess skin;
• Grade 2a: moderate breast enlargement with no excess skin;
• Grade 2b: moderate breast enlargement with excess skin;
• Grade 3: marked breast enlargement with excess skin.
Patients with grades 1 and 2a gynaecosmastia require no skin
excision, but the breast development associated with grades 2b and 3 is so
marked that excess skin must be removed. Although this classification is
not applicable to the surgical management of men with breast cancer and
gynaecomastia, it allows important management decisions to be made for the
surgical correction of gynaecomastia.
1 Niewoehner CB, Schorer AE. Gynaecomastia and breast cancer in men.
BMJ 2008;336:709-13.
2 Simon BE, Hoffman S, Kahn S. Classification and surgical correction
of gynecomastia. Plast Reconstr Surg 1973;51:48-52.
Competing interests:
None declared
Competing interests: No competing interests
Niewoehner and Schorer’s review of breast cancer in men was thorough
and informative, but may have under-emphasised the role of antipsychotic
medication as a causal mechanism of hyperprolactinaemia. An increase in
serum prolactin is a class effect of all antipsychotic medication, due to
dopamine antagonism. ‘Typical’ antipsychotics (chlorpromazine,
haloperidol) commonly induce elevations above the normal range, as do some
of the newer antipsychotics, most notably risperidone (which is mentioned
in the article) and amisulpride (which is not). Some 60 % of women and 40%
of men treated with conventional or ‘prolactin raising’ antipsychotics
will develop a prolactin level above the normal range; tenfold increases
from baseline are possible (1,2). It is so common that a measurement of
serum prolactin has been advocated as a useful guide to compliance
(Maudsley Prescribing Guidelines 2005-2006) when ‘older, typical’
antipsychotics are used. In women, studies have (admittedly
inconsistently) shown an increased rate of breast cancer (3), and this
article notes that ‘the Food and Drug Administration has required product
label warnings for conventional neuroleptics since the 1970s based on a
possible association with breast cancer’.
There are at least two case reports of breast cancer in men with
hyperprolactinaemia (4,5), although in neither case was elevated prolactin
due to treatment with antipsychotic medication. However, one factor which
has bedevilled the studies searching for, and sometimes finding, the
association with breast cancer and antipsychotic medication in women has
been the time lag between treatment, prolactin elevation, and illness.
Atypical antipsychotics, in particular risperidone, are being prescribed
more frequently in an ever younger age group, as adjuncts to the treatment
of ADHD, autism, and persistent aggression (all off licence). They are
also in use as part of the move towards early intervention in psychosis,
and the current recommendations are that treatment be continued for a
period of years (6), if not indefinitely. We know almost nothing about the
effects of hyperprolactinaemia starting in adolescence on the risk of
breast cancer; other effects, such as that on bone density, are only now
being fully recognised (7). The effects of long term hyperprolactinaemia
in men also require further study; this article was a useful reminder of
one more potential risk.
References:
1) A.Wieck and P. M. Haddad; Antipsychotic-induced hyperprolactinaemia in
women: pathophysiology, severity and consequences; selective literature
review British Journal of Psychiatry (2003), 182 , 199- 204
2) P. M. Haddad, A. Wieck; Antipsychotic-induced hyperprolactinaemia:
mechanisms, clinical features and management. Drugs, 2004, vol. 64, no.
20, p. 2291−314
3) Philip S. Wang, MD, DrPH; Alexander M. Walker, MD, DrPH; Ming T.
Tsuang, MD, PhD, DSc; E. John Orav, PhD; Robert J. Glynn, PhD, ScD; Raisa
Levin, MS; Jerry Avorn, MD Dopamine Antagonists and the Development of
Breast Cancer Arch Gen Psychiatry. 2002;59:1147-1154
4) Forloni−F, Giovilli−M, Pecis−C,
Bortolani−E, Preziosi−A, Barzaghi−M−E,
Corti−D, Beck−Peccoz−P. Pituitary
prolactin−secreting macroadenoma combined with bilateral breast
cancer in a 45-year-old male; Journal of endocrinological investigation,
Jun 2001, vol. 24, no. 6, p. 454−9
5) Gola−M, Papi−G, Tavernari−V, Pesenti−M,
Ficarra−G, Velardo−A (Mammary carcinoma in a patient with
hyperprolactinemia). Minerva endocrinologica, Dec 1997, vol. 22, no. 4, p.
107−10
6) NICE guidelines for schizophrenia:
http://www.nice.org.uk/nicemedia/pdf/CG1NICEguidelineoster.pdf
7) A.M.Meaney, S. Smith,O. D. Howes, M.O’Brien, R. M. Murray and
V.O’Keane; Effects of long-term prolactin-raising antipsychotic medication
on bonemineral density in patients
with schizophrenia, British Journal of Psychiatry (2004), 184 , 503-508
Competing interests:
None declared
Competing interests: No competing interests
Whilst Niewoehner and Schorer note in their review of gynaecomastia
and
breast cancer in men that the use of anabolic steroids should be
considered
in the cause of gynecomastia [1], it is important to recognise the
significant
levels of use of these drugs for performance- and image-enhancing reasons
within the general population [2, 3, 4]. Furthermore, many users practice
complex, self-directed, polydrug regimes [2, 3, 5] that include not only
the
use of supraphysiologic doses of multiple types of anabolic steroids but
also,
inter alia, growth hormone, human chorionic gonadotropin, spironolactone
and a wide variety of supplements (e.g. the prohormone
dehydroepiandrosterone (DHEA)) [2, 3, 5, 6] — substances that have all
been
associated with gynecomastia.
Given the high levels of self-reported gynecomastia in users [3] —
and
reflected in the widespread prophylactic use of self-prescribed tamoxifen
[3,
6], (and, anecdotally, an increasing use of aromatase inhibitors) — we
consider it particularly relevant to ask about use of anabolic steroids
and
ancillary substances (type of drugs, dose and duration of use) in
individuals
presenting with gynecomastia who have mesomorphic or hypermesomorphic
body types (in this regard it is also noteworthy that use of these drugs
is not
just restricted to adolescents and those in their 20s [2, 3, 6]).
As the authors of the review highlight, however, patients can feel
embarrassed and anxious by their condition and this can be compounded in
this population given the demonisation of anabolic steroids by society.
Further, the historic low-level of engagement and trust by this population
with health professionals [2, 3] may act on this, which could increase a
reluctance to reveal their use of these substances [7, 8]. Alongside this,
clinicians should also be cognisant to the ubiquity of counterfeit drugs
in use
by this population, which, not only differ in stated dose and drug, but
also
contain other substances not present on the labelling [9–11]. This,
ultimately,
may confound determination of the causative substance/agent.
Finally, alongside the risk of gynaecomastia, it is important to
recognise that
this population have complex health needs [2, 3, 5, 12], not least added
to by
the fact that more than 70% of these individuals inject many of these
drugs
[2, 3]. Yet, aside from the provision of sterile injecting equipment,
there are
few opportunities for this population to engage with health professionals.
From both the literature [2, 3] and our own experience of working with
this
population there are clearly a significant number of individuals who
desire
better engagement with health services. We would therefore suggest that we
need to explore new ways of engaging with this population that are
acceptable to them in order to reduce harm and promote health.
1. Niewoehner CB, Schorer AE. Gynaecomastia and breast cancer in men.
BMJ.
2008;336(7646):709-713.
2. Korkia P, Stimson GV. Anabolic steroid use in Great Britain: an
exploratory
investigation. A report to the Department of Health, the Welsh Office and
the
Chief Scientist Office, Scottish Home and Health Department. London,
United
Kingdom: Her Majesty’s Stationery Office, 1993.
3. Lenehan P, Bellis M, McVeigh J. Anabolic steroid use in the North
West of
England. Journal of Performance Enhancing Drugs. 1996;1:57–70.
4. Roe S, Man L. Drug misuse declared: Findings from the 2006/07
British
Crime Survey. London, United Kingdom: Home Office; 2007.
5. Dawson RT. Drugs in sport – the role of the physician. J
Endocrinol.
2001;170:55-61.
6. Baker JS, Graham MR, Davies B. Steroid and prescription medicine
abuse in
the health and fitness community: A regional study. Eur J Intern Med.
2006;17(7):479–484.
7. van der Kuy PH, Stegeman A, Looij BJ Jr, Hooymans PM.
Falsification of Thai
dianabol. Pharm World Sci. 1997;19(4):208–209.
8. Ferenchick GS. Validity of self-report in identifying anabolic
steroid use
among weightlifters. J Gen Intern Med. 1996;11(9):554-556.
9. McVeigh J, Lenehan P. Counterfeits and fakes: a growing problem.
Relay.
1994;1(1):8–9.
10. Perry H. Counterfeit-fake anabolic steroids and hazards of their
use.
Relay. 1995;1(4):9-12.
11. Musshoff F, Daldrup T, Ritsch M. [Anabolic steroids on the German
black
market]. Arch Kriminol. 1997;199(5-6):152–158.
12. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in
athletes. Sports Med. 2004;34(8):513-554.
Competing interests:
None declared
Competing interests: No competing interests
I would like to expand on the thoughtful review on gynecomastia by
Niewoehner et al. 1
Examination of the testis is mandatory in all patients consulting for this
sign. Location, size and turgor of the gonads provide invaluable
information on the status of the hypothalamic pituitary testicular axis;
subsequent tests could be prioritized based on this evaluation.2
Although idiopathic gynecomastia is highly prevalent with hundred of
million of affected men, unfortunately, there is no proven medical therapy
for this condition and the quality of the research using medications is
very poor. As an example, the best publications available, for tamoxifen
include only 332 individuals and of those only 10 (<_3 were="were" studied="studied" in="in" randomized="randomized" trials.="trials." _3the="_3the" literature="literature" showing="showing" efficacy="efficacy" for="for" all="all" other="other" drugs="drugs" is="is" smaller="smaller" and="and" as="as" unreliable="unreliable" mostly="mostly" due="due" to="to" lack="lack" of="of" proper="proper" controls.="controls." given="given" this="this" uncertainty="uncertainty" it="it" problematic="problematic" draw="draw" conclusions="conclusions" regarding="regarding" the="the" use="use" any="any" medication="medication" treatment="treatment" gynecomastia.="gynecomastia." p="p"/> Saul Malozowski, MD, PhD, MBA
Rockville, MD 20852
malozowskis@hotmail.com
References
1) Niewoehner CB, Schorer AE. BMJ 2008; 336:709-13
2) Santen RJ. Gynecomastia. In: DeGroot LJ and Jameson JL, eds.
Endocrinology. 4th ed. Philadelphia, USA: WB Sounders, 2001:2335-43.
3) Braunstein GD. Gynecomastia. N Engl J Med, 2007;357:1229-37.
Competing interests:
None declared
Competing interests: No competing interests
Dear Editor,
We read with interest the clinical review article written by
Niewoehner CB, Schorer AE titled Gynaecomastia and breast cancer in men.
Surgery for benign gynaecomastia in the UK has risen by 27% in 2007 in
comparison to 2006.1 In men with benign gynaecomastia, surgical excision
is considered to be a low priority aesthetic procedure. In some regions
men with benign gynaecomastia would not be offered surgical treatment on
the NHS. 2 In our region regional guidelines from 2006 suggest that 200
grams of tissue should be excised from each side to warrant surgery on the
NHS.3 We carried out an audit of 48 men who underwent surgery for benign
gynaecomastia on the NHS between 2003 and 2006, prior to the publication
of the guidelines. Only 6.25% would have met the priorities committee
guidelines for surgery on the NHS. We wonder whether the government
guidelines for surgery for benign gynaecomastia are realistic.
Luke Jones, ST2 Surgery Oxford Rotation
Negin Shamsian, Specialist Registrar Plastic, and Reconstructive Surgery,
Oxford Rotation
Sudip Ghosh, Consultant Plastic, Reconstructive and Burns Surgeon, Stoke
Mandeville Hospital, Aylesbury
Contributors: NS and LJ carried out audit entitled A retrospective
review of gynaecomastia - weights of tissue excised in 2007, Roger
Ramcharan and Peter Budny were contributors on this audit.
Competing interests: as above
References
1. BAAPS Statistics 2007.
http://www.baaps.org.uk/content/view/280/62/
2. Oxfordshire NHS Trust Priorities Forum Policy statement -
http://www.oxfordshire.nhs.uk/docs/lavender/policy6b2.pdf
3. Thames Valley Priorities Committee Plastic Surgery Guidelines on
Gynaecomastia
Miss N Shamsian
Specialist Registrar Plastic Surgery
neginshamsian@yahoo.com
Competing interests:
NS and LJ completed a gynaecomastia audit entitled A Retrospective review of Gynaecomastia surgery and weights of tissue excision in 2007.
Competing interests: No competing interests
This article fails to mention the long list of drugs which can be
associated with gynaecomastia,especially in the elderly.A list(produced by
the Pharmacy of the Norfolk and Norwich University Hospital in 1993)has 69
drugs on it, including the commomly prescribed drugs
allupurinol, amitriptylline, atenolol, ciprofloxacin, chlorpromazine, digoxin, enalapril, furosamide,nifedipine,
verapamil and warfarin (the list is far too long to be included in a
letter).In clinical practice medication is the commonest cause of
gynaecomastia in the elderly.
One important point in technique should also be mentioned in removing
excess breast tissue in young men, is that if all the abnormal breast
tissue is excised there will be an unsatisfactory cosmetic outcome as the
enlarged breast will be replaced by a dent.A sufficient slice of breast
tissue should be left to prevent this happening, and I have never
encountered recurrent gynaecomastia despite adopting this technique over
many years.
Competing interests:
None declared
Competing interests: No competing interests
Re: Gynaecomastia and breast cancer in men
Gynecomastia is not cancerous; however, males who have it are at
higher risk of developing breast cancer because it can be the result of a
hormonal imbalance.
Male breast cancer is most common among those 60 and older, because
the breasts tend to become enlarged with age. As with women, hormonal
changes play a key role in the development of the disease -- men with
higher than normal estrogen activity are at greater risk.
In younger males and older men, breast cancer is typically associated
with gynecomastia, a condition that results in overdeveloped breasts. It
can be caused by high estrogen levels or certain medications and steroids.
Competing interests:
None declared
Competing interests: No competing interests